循环microRNAs作为潜在的肝脏相关疾病标记物的初步研究
|
摘要
非编码RNA (non-coding RNA, ncRNA)是当前生命科学研究的前沿热点之一,其中,microRNAs (miRNAs)是一大类新型的、细胞内源性的单链非编码小RNA,由基因组中的miRNA基因(miRNAs genes)编码。成熟miRNAs的平均长度约22 nt,广泛分布于各种生命体,作为RNA诱导的沉默复合体(RNA-induced silencing complex, RISC)的核心功能要素之一,主要通过与其靶mRNA (messenger RNA, mRNA)的3'-UTR区(3'-untranslated region,3'-UTR)互补结合,进而抑制mRNA的翻译或诱导mRNA降解,发挥RNA介导的转录后基因沉默(post-transcriptional gene silencing, PTGS)效应,对细胞增殖、分化、凋亡等一系列生命现象发挥广泛的生物学调控作用。
据生物信息学预测,人类基因组编码的miRNAs可能超过1000种。研究发现,在不同的生理病理状态下,组织、细胞的miRNAs表达谱具有独特的时空特异性和组织特异性,miRNAs异常表达调控与肿瘤等多种人类疾病的发生发展密切相关。最近研究显示,血浆或血清中的循环miRNAs (circulating miRNAs, cir-miRNAs)可能是一类具有潜在临床应用价值的新型生物标志物(biomarker)。业已表明,肿瘤、心血管病等疾患个体的血浆或血清中存在如miR-92和miR-1等一些异常表达的、可能有助于疾病诊断及预后评估的循环miRNAs。
基于目前循环miRNAs的研究新进展,我们有理由推测：在正常机能状态下,机体内循环miRNAs的种类及其表达丰度可能处于一个相对稳定、平衡的状态,而机体内器官组织的功能、代谢异常或器质性病变等因素可能会直接或间接地破坏机体内循环miRNAs的稳态(homeostasis),表现为特定生理或疾病状态下某些循环miRNAs的表达水平的变化。
乙型肝炎病毒(hepatitis B virus, HBV)感染、慢性乙型肝炎(chronic hepatitis B,CHB)(简称慢性乙肝)、肝纤维化(liver fibrosis,LF)、肝硬化(livercirrhosis, LC)和肝细胞癌(hepatocelluler carcinoma, HCC)等肝脏疾病(简称肝病)依旧严重危害人们身体健康,进一步发展更加特异、敏感的肝脏疾病生物标志物可以弥补ALT、AST、AFP等传统血清学标志物的不足,对于提高肝脏相关疾病的辅助诊断、评估及健康管理等具有十分重要的临床意义。
因此,为探索循环miRNAs对于肝脏相关疾病辅助诊断的潜在意义,本论文主要进行了四个方面的工作：第一,建立利用实时定量PCR (real-time quantitative PCR, rt-qPCR)对临床血清标本中循环miRNAs进行定量测定的技术平台。第二,采用基于qPCR (quantitative PCR)的TaqMan低密度阵列(TaqMan low density array, TLDA)技术,对健康个体、肝细胞癌(HCC)和肝硬化(LC)患者血清参考标本中的循环miRNAs进行了初步分析,以期筛选潜在的肝脏疾病相关的循环miRNAs。第三,通过分析筛选结果,选择5种在HCC和LC血清中表达上调的、可能与肝脏疾病相关的miRNAs(即miR-146a,-215,-224,-573-3p和miR-885-5p)进行初步验证。第四,基于有关文献进行数据挖掘,分析miR-885-5p在不同人体组织中的表达及分布,进一步采用TargetScan等生物信息学软件对miR-885-5p的潜在靶基因进行预测和分析。主要获得以下四个方面的结果：第一,建立了循环miRNAs定量的技术路线。第二,验证了TLDA技术用于循环miRNAs筛选的可行性。第三,发现慢性乙型肝炎、肝硬化及肝细胞癌患者血清中miR-885-5p的表达丰度显著升高。ROC (receiver operating characteristic, ROC)分析显示,miR-885-5p用于鉴别肝脏相关疾病与健康个体时的曲线下面积(the area under curve,AUC)为0.904,特异性为79.17%,敏感性为90.53%。最后,基于文献分析,发现miR-885-5p在肝脏组织中具有较高的表达水平。生物信息学分析显示,在胆固醇逆向转运(cholesterol reverse transport, CRT)及磷脂等脂类代谢中具有重要功能的ATP结合盒转运体超家族成员ABCA1 (ATP-binding cassette sub-family A member 1, ABCA1)是miR-885-5p的潜在靶基因之一。
本论文建立的技术平台可为循环miRNAs的实时定量提供参考,发现并初步验证了血清miR-885-5p可能是一种有助于肝脏疾病诊断的新型标志物。
Non-coding RNA (ncRNA) including microRNAs (miRNAs) have currently become one of the frontiers and hotspots of life science. MiRNAs are a large class of single-strand endogenous non-coding small RNA of approximately 22 nucleotides (nt) in length that encoded by miRNAs genes in genome and found in a wide varity of organisms. In recent years, it was uncovered that mature miRNAs function as one of the key components of RNA-induced silencing complex (RISC) to perform their post-trancriptional gene silencing (PTGS) effects, by binding to specific sites in the 3'-untranslated region (3'-UTR) of messenger RNAs (mRNAs) and then inhibiting the translation or inducing the degradation of mRNAs, and play ubiquitous roles in gene expression regulation contributing to diverse cellular processes such as cellular development, differentiation and apoptosis, etc.
It was predicted bioinformatically that there exist more than 1000 miRNAs in human genome. The tempo-spatiality specific and tissue-specific expression patterns of miRNAs in different tissues/cells in various physiopathological conditions were well documented, and deregulated miRNAs expressions were consistently observed to involve in the initiations and developments of many diseases including human cancer. More recently, miRNAs in plasma/serum are emerging as a new class of potential biomarkers for minimally invasive diagnosis and monitoring of patients with several diseases such as cancer and cardiovascular disease. For instance, it was found that there are some abberrantly up-regulated miRNAs, such as miR-92 and miR-1, in the plasma and/or serum samples of patients with cancers or cardiovascular diseases, and therefore circulating miRNAs may serve as potential biomarkers for the diagnosis and prognosis of corresponding clinical conditions.
Considering recent progresses in circulating miRNAs research field, we could speculate that the species and levels of miRNAs in plasma and/or serum may be maintained in homeostatic status under normal physiological conditions, however, if there are functional and/or metabolic abnormality or organ injuries in human body, the homeostasis of circulating miRNAs may be altered directly or indirectly and therefore result in various degree of variations of specific circulating miRNAs levels in blood.
Currently, liver-related diseases such as hepatitis B virus (HBV) infection, chronic hepatitis B (CHB), liver fibrosis (LF), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), etc, are still significant threats to human health worldwide. Therefore, it is still necessary to develop more specific and sensitive biomarkers to complement the traditional markers, such as ALT, AST and AFP, etc, to improve the diagnosis, assessment and health management of patients with liver pathologies.
To investigate the feasibility of explorating circulating miRNAs as potential markers for the diagnosis of liver-related diseases, the present work firstly established the platform for quantifing circulating miRNAs in clinical serum samples by using real-time quantitative PCR (rt-qPCR). Thereafter, the quantitative PCR-based TaqMan low density arrays (TLDA) were employed to characterize the circulating miRNAs in the serum samples of normal control, HCC and LC patients, respectively, to investigate whether there are deregulated miRNAs in sera of patients with of liver-related diseases. Furthermore, five up-regulated miRNAs in HCC and LC serum samples, i.e. miR-146a,-215,-224,-574-3p and miR-885-5p were selected and validated in independent case-control studies. Finally, data mining based on a newly published literature was performed to understand the tissue distribution of miR-885-5p and the potential targets of miR-885-5p were predicted and analyzed by using bioinformatics softwares such as TargetScan, etc. This work achieves four main results. Firstly, Circulating miRNAs quantification platform is established in our Lab successfully. Second, The feasibility of using TLDA to quantify circulating miRNAs is evaluated. Third, Circulating miR-885-5p is found to be significantly increased in the serum samples of patients with HCC, CHB and LC, respectively. More importantly, miR-885-5p yield an AUC (area under the curve) of 0.904 in discriminating patients with liver pathologies from normal control, with specificity of 79.17% and sensitivity of 90.53%, respectively. Finally, data mining based on a newly published literature reveals that miR-885-5p is a relatively liver tissue-restricted miRNAs. Furthermore, bioinformatics analysis indicates that the ABCA1 (ATP-binding cassette sub-family A member 1, ABCA1), functioning as the gatekeeper of cholesterol reverse transport (CRT) and key modulator in phosphatide metabolism, is one of the potential targets of miR-885-5p.
In summary, the technical platform established here can serve as reference for similar research related to miRNAs quantification, and more importantly, circulating miR-885-5p in serum may serve as a potential biomarker for liver-related diseases detection.
据生物信息学预测,人类基因组编码的miRNAs可能超过1000种。研究发现,在不同的生理病理状态下,组织、细胞的miRNAs表达谱具有独特的时空特异性和组织特异性,miRNAs异常表达调控与肿瘤等多种人类疾病的发生发展密切相关。最近研究显示,血浆或血清中的循环miRNAs (circulating miRNAs, cir-miRNAs)可能是一类具有潜在临床应用价值的新型生物标志物(biomarker)。业已表明,肿瘤、心血管病等疾患个体的血浆或血清中存在如miR-92和miR-1等一些异常表达的、可能有助于疾病诊断及预后评估的循环miRNAs。
基于目前循环miRNAs的研究新进展,我们有理由推测：在正常机能状态下,机体内循环miRNAs的种类及其表达丰度可能处于一个相对稳定、平衡的状态,而机体内器官组织的功能、代谢异常或器质性病变等因素可能会直接或间接地破坏机体内循环miRNAs的稳态(homeostasis),表现为特定生理或疾病状态下某些循环miRNAs的表达水平的变化。
乙型肝炎病毒(hepatitis B virus, HBV)感染、慢性乙型肝炎(chronic hepatitis B,CHB)(简称慢性乙肝)、肝纤维化(liver fibrosis,LF)、肝硬化(livercirrhosis, LC)和肝细胞癌(hepatocelluler carcinoma, HCC)等肝脏疾病(简称肝病)依旧严重危害人们身体健康,进一步发展更加特异、敏感的肝脏疾病生物标志物可以弥补ALT、AST、AFP等传统血清学标志物的不足,对于提高肝脏相关疾病的辅助诊断、评估及健康管理等具有十分重要的临床意义。
因此,为探索循环miRNAs对于肝脏相关疾病辅助诊断的潜在意义,本论文主要进行了四个方面的工作：第一,建立利用实时定量PCR (real-time quantitative PCR, rt-qPCR)对临床血清标本中循环miRNAs进行定量测定的技术平台。第二,采用基于qPCR (quantitative PCR)的TaqMan低密度阵列(TaqMan low density array, TLDA)技术,对健康个体、肝细胞癌(HCC)和肝硬化(LC)患者血清参考标本中的循环miRNAs进行了初步分析,以期筛选潜在的肝脏疾病相关的循环miRNAs。第三,通过分析筛选结果,选择5种在HCC和LC血清中表达上调的、可能与肝脏疾病相关的miRNAs(即miR-146a,-215,-224,-573-3p和miR-885-5p)进行初步验证。第四,基于有关文献进行数据挖掘,分析miR-885-5p在不同人体组织中的表达及分布,进一步采用TargetScan等生物信息学软件对miR-885-5p的潜在靶基因进行预测和分析。主要获得以下四个方面的结果：第一,建立了循环miRNAs定量的技术路线。第二,验证了TLDA技术用于循环miRNAs筛选的可行性。第三,发现慢性乙型肝炎、肝硬化及肝细胞癌患者血清中miR-885-5p的表达丰度显著升高。ROC (receiver operating characteristic, ROC)分析显示,miR-885-5p用于鉴别肝脏相关疾病与健康个体时的曲线下面积(the area under curve,AUC)为0.904,特异性为79.17%,敏感性为90.53%。最后,基于文献分析,发现miR-885-5p在肝脏组织中具有较高的表达水平。生物信息学分析显示,在胆固醇逆向转运(cholesterol reverse transport, CRT)及磷脂等脂类代谢中具有重要功能的ATP结合盒转运体超家族成员ABCA1 (ATP-binding cassette sub-family A member 1, ABCA1)是miR-885-5p的潜在靶基因之一。
本论文建立的技术平台可为循环miRNAs的实时定量提供参考,发现并初步验证了血清miR-885-5p可能是一种有助于肝脏疾病诊断的新型标志物。
Non-coding RNA (ncRNA) including microRNAs (miRNAs) have currently become one of the frontiers and hotspots of life science. MiRNAs are a large class of single-strand endogenous non-coding small RNA of approximately 22 nucleotides (nt) in length that encoded by miRNAs genes in genome and found in a wide varity of organisms. In recent years, it was uncovered that mature miRNAs function as one of the key components of RNA-induced silencing complex (RISC) to perform their post-trancriptional gene silencing (PTGS) effects, by binding to specific sites in the 3'-untranslated region (3'-UTR) of messenger RNAs (mRNAs) and then inhibiting the translation or inducing the degradation of mRNAs, and play ubiquitous roles in gene expression regulation contributing to diverse cellular processes such as cellular development, differentiation and apoptosis, etc.
It was predicted bioinformatically that there exist more than 1000 miRNAs in human genome. The tempo-spatiality specific and tissue-specific expression patterns of miRNAs in different tissues/cells in various physiopathological conditions were well documented, and deregulated miRNAs expressions were consistently observed to involve in the initiations and developments of many diseases including human cancer. More recently, miRNAs in plasma/serum are emerging as a new class of potential biomarkers for minimally invasive diagnosis and monitoring of patients with several diseases such as cancer and cardiovascular disease. For instance, it was found that there are some abberrantly up-regulated miRNAs, such as miR-92 and miR-1, in the plasma and/or serum samples of patients with cancers or cardiovascular diseases, and therefore circulating miRNAs may serve as potential biomarkers for the diagnosis and prognosis of corresponding clinical conditions.
Considering recent progresses in circulating miRNAs research field, we could speculate that the species and levels of miRNAs in plasma and/or serum may be maintained in homeostatic status under normal physiological conditions, however, if there are functional and/or metabolic abnormality or organ injuries in human body, the homeostasis of circulating miRNAs may be altered directly or indirectly and therefore result in various degree of variations of specific circulating miRNAs levels in blood.
Currently, liver-related diseases such as hepatitis B virus (HBV) infection, chronic hepatitis B (CHB), liver fibrosis (LF), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), etc, are still significant threats to human health worldwide. Therefore, it is still necessary to develop more specific and sensitive biomarkers to complement the traditional markers, such as ALT, AST and AFP, etc, to improve the diagnosis, assessment and health management of patients with liver pathologies.
To investigate the feasibility of explorating circulating miRNAs as potential markers for the diagnosis of liver-related diseases, the present work firstly established the platform for quantifing circulating miRNAs in clinical serum samples by using real-time quantitative PCR (rt-qPCR). Thereafter, the quantitative PCR-based TaqMan low density arrays (TLDA) were employed to characterize the circulating miRNAs in the serum samples of normal control, HCC and LC patients, respectively, to investigate whether there are deregulated miRNAs in sera of patients with of liver-related diseases. Furthermore, five up-regulated miRNAs in HCC and LC serum samples, i.e. miR-146a,-215,-224,-574-3p and miR-885-5p were selected and validated in independent case-control studies. Finally, data mining based on a newly published literature was performed to understand the tissue distribution of miR-885-5p and the potential targets of miR-885-5p were predicted and analyzed by using bioinformatics softwares such as TargetScan, etc. This work achieves four main results. Firstly, Circulating miRNAs quantification platform is established in our Lab successfully. Second, The feasibility of using TLDA to quantify circulating miRNAs is evaluated. Third, Circulating miR-885-5p is found to be significantly increased in the serum samples of patients with HCC, CHB and LC, respectively. More importantly, miR-885-5p yield an AUC (area under the curve) of 0.904 in discriminating patients with liver pathologies from normal control, with specificity of 79.17% and sensitivity of 90.53%, respectively. Finally, data mining based on a newly published literature reveals that miR-885-5p is a relatively liver tissue-restricted miRNAs. Furthermore, bioinformatics analysis indicates that the ABCA1 (ATP-binding cassette sub-family A member 1, ABCA1), functioning as the gatekeeper of cholesterol reverse transport (CRT) and key modulator in phosphatide metabolism, is one of the potential targets of miR-885-5p.
In summary, the technical platform established here can serve as reference for similar research related to miRNAs quantification, and more importantly, circulating miR-885-5p in serum may serve as a potential biomarker for liver-related diseases detection.
引文
1. Gaffney, D.J. and P.D. Keightley, Unexpected conserved non-coding DNA blocks in mammals. Trends Genet,2004.20(8):p.332-7.
2. Bird, C.P., B.E. Stranger, and E.T. Dermitzakis, Functional variation and evolution of non-coding DNA. Curr Opin Genet Dev,2006.16(6):p. 559-64.
3. Subirana, J.A. and X. Messeguer, The most frequent short sequences in non-coding DNA. Nucleic Acids Res,2010.38(4):p.1172-81.
4. Kurth, H.M. and K. Mochizuki, Non-coding RNA:a bridge between small RNA and DNA. RNA Biol,2009.6(2):p.138-40.
5. Micro RNA and non-coding DNA and repeats. Genomic Med,2008.2(3-4): p.205-7.
6. Mattick, J.S. and I.V. Makunin, Non-coding RNA. Hum Mol Genet,2006. 15 Spec No 1:p.R 17-29.
7. Nelson, P., et al., The microRNA world:small is mighty. Trends Biochem Sci,2003.28(10):p.534-40.
8. Eddy, S.R., Non-coding RNA genes and the modern RNA world. Nat Rev Genet,2001.2(12):p.919-29.
9. Bartel, D.P., MicroRNAs:genomics, biogenesis, mechanism, and function. Cell,2004.116(2):p.281-97.
10. O'Hara, S.P., et al., MicroRNAs:key modulators of posttranscriptional gene expression. Gastroenterology,2009.136(1):p.17-25.
11. Bartel, D.P., MicroRNAs:target recognition and regulatory functions. Cell, 2009.136(2):p.215-33.
12. Leung, A.K. and P.A. Sharp, microRNAs:a safeguard against turmoil? Cell, 2007.130(4):p.581-5.
13. Ferdin, J., T. Kunej, and G.A. Calin, Non-coding RNAs:identification of cancer-associated microRNAs by gene profiling. Technol Cancer Res Treat, 2010.9(2):p.123-38.
14. Paranjape, T., F.J. Slack, and J.B. Weidhaas, MicroRNAs:tools for cancer diagnostics. Gut,2009.58(11):p.1546-54.
15. Cho, W.C., MicroRNAs in cancer-from research to therapy. Biochim Biophys Acta,2010.1805(2):p.209-217.
16. Oulas, A., M. Reczko, and P. Poirazi, MicroRNAs and cancer-the search begins! IEEE Trans Inf Technol Biomed,2009.13(1):p.67-77.
17. O'Connell, R.M., et al., Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol,2010.10(2):p.111-22.
18. Harris, A., S.M. Krams, and O.M. Martinez, MicroRNAs as Immune Regulators:Implications for Transplantation. Am J Transplant,2010.
19. Lau, P. and B. de Strooper, Dysregulated microRNAs in neurodegenerative disorders. Semin Cell Dev Biol,2010.
20. Scalbert, E. and A. Bril, Implication of microRNAs in the cardiovascular system. Curr Opin Pharmacol,2008.8(2):p.181-8.
21. Small, E.M., R.J. Frost, and E.N. Olson, MicroRNAs add a new dimension to cardiovascular disease. Circulation,2010.121(8):p.1022-32.
22. Li, S., et al., Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J Lipid Res,2009.50(9):p.1756-65.
23. Jeffrey, S.S., Cancer biomarker profiling with microRNAs. Nat Biotechnol, 2008.26(4):p.400-1.
24. Lu, J., et al., MicroRNA expression profiles classify human cancers. Nature, 2005.435(7043):p.834-8.
25. Iorio, M.V., et al., MicroRNA gene expression deregulation in human breast cancer. Cancer Res,2005.65(16):p.7065-70.
26. Rosenfeld, N., et al., MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol,2008.26(4):p.462-9.
27. Voorhoeve, P.M., MicroRNAs:Oncogenes, tumor suppressors or master regulators of cancer heterogeneity? Biochim Biophys Acta,2010.1805(1):p. 72-86.
28. Couzin, J., MicroRNAs make big impression in disease after disease. Science,2008.319(5871):p.1782-4.
29. Lawrie, C.H., et al., Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol,2008.141(5):p.672-5.
30. Mitchell, P.S., et al., Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A,2008.105(30):p.10513-8.
31. Chen, X., et al., Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res,2008. 18(10):p.997-1006.
32. Ng, E.K., et al., Differential expression of microRNAs in plasma of patients with colorectal cancer:a potential marker for colorectal cancer screening. Gut,2009.58(10):p.1375-81.
33. Huang, Z., et al., Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer,2009.
34. Heneghan, H.M., et al., Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg,2010.251(3):p.499-505.
35. Zhu, W., et al., Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes,2009.2:p.89.
36. Heneghan, H.M., et al., MicroRNAs as Novel Biomarkers for Breast Cancer. J Oncol,2009.2009:p.950201.
37. Tsujiura, M., et al., Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer,2010.
38. Ji, X., et al., Plasma miR-208 as a biomarker of myocardial injury. Clin Chem,2009.55(11):p.1944-9.
39. Ai, J., et al., Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun,2010.391(1): p.73-7.
40. Tijsen, A.J., et al., MiR423-5p As a Circulating Biomarker for Heart Failure. Circ Res,2010.
41. Wang, K., et al., Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A,2009.106(11):p. 4402-7.
42.慢性乙型肝炎抗病毒治疗专家委员会.慢性乙型肝炎抗病毒治疗专家共识.中华实验和临床感染病杂志.2010.4(1)：p.82-91.
43. Tan, L.P., et al., miRNA profiling of B-cell subsets:specific miRNA profile for germinal center B cells with variation between centroblasts and centrocytes. Lab Invest,2009.89(6):p.708-16.
44. Zhang, J., et al., Patterns of microRNA expression characterize stages of human B-cell differentiation. Blood,2009.113(19):p.4586-94.
45. Bartels, C.L. and G.J. Tsongalis, MicroRNAs:novel biomarkers for human cancer. Clin Chem,2009.55(4):p.623-31.
46. El-Hefnawy, T., et al., Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics. Clin Chem,2004. 50(3):p.564-73.
47. Wang, J., et al., MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila Pa),2009.2(9):p.807-13.
48. Gilad, S., et al., Serum microRNAs are promising novel biomarkers. PLoS One,2008.3(9):p. e3148.
49. Jung, M., et al., Robust MicroRNA Stability in Degraded RNA Preparations from Human Tissue and Cell Samples. Clin Chem,2010.
50. Li, J., et al., Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells. BMC Biotechnol,2007.7:p.36.
51. Wang, G.K., et al., Circulating microRNA:a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J,2010. 31(6):p.659-66.
52. Cheng, Y., et al., A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond),2010.119(2):p.87-95.
53. Valadi, H., et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol,2007. 9(6):p.654-9.
54. Taylor, D.D. and C. Gercel-Taylor, MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol,2008. 110(1):p.13-21.
55. van Niel, G., et al., Exosomes:a common pathway for a specialized function. J Biochem,2006.140(1):p.13-21.
56. Simpson, R.J., et al., Exosomes:proteomic insights and diagnostic potential. Expert Rev Proteomics,2009.6(3):p.267-83.
57. Chen, C., et al., Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res,2005.33(20):p. e179.
58. Shingara, J., et al., An optimized isolation and labeling platform for accurate microRNA expression profiling. RNA,2005.11(9):p.1461-70.
59. Liu, C.G., et al., MicroRNA expression profiling using microarrays. Nat Protoc,2008.3(4):p.563-78.
60. Yin, J.Q., R.C. Zhao, and K.V. Morris, Profiling microRNA expression with microarrays. Trends Biotechnol,2008.26(2):p.70-6.
61. Huang, X.H., et al., Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma:miR-338 is downregulated. Hepatol Res,2009.39(8):p.786-94.
62. Hu, Z., et al., Serum MicroRNA Signatures Identified in a Genome-Wide Serum MicroRNA Expression Profiling Predict Survival of Non-Small-Cell Lung Cancer. J Clin Oncol,2010.
63. Tang, F., et al.,220-plex microRNA expression profile of a single cell. Nat Protoc,2006.1(3):p.1154-9.
64. Wang, X., A PCR-based platform for microRNA expression profiling studies. RNA,2009.15(4):p.716-23.
65.徐洁等.肝脏特异性miR-122的分子生物学特性及功能.生物物理学报,2009.25(3)：p.183-191.
66. Esau, C., et al., miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab,2006.3(2):p.87-98.
67. Su, H., et al., MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res,2009.69(3): p.1135-42.
68. Murakami, Y., et al., Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene, 2006.25(17):p.2537-45.
69. Schmittgen, T.D. and K..J. Livak, Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc,2008.3(6):p.1101-8.
70. Sato, F., et al., Intra-platform repeatability and inter-platform comparability of microRNA microarray technology. PLoS One,2009.4(5):p. e5540.
71. Cortez, M.A. and G.A. Calin, MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther,2009. 9(6):p.703-711.
72. Lu, B., et al., TaqMan low density array is roughly right for gene expression quantification in colorectal cancer. Clin Chim Acta,2008.389(1-2):p. 146-51.
73. Satih, S., et al., Expression analyses of nuclear receptor genes in breast cancer cell lines exposed to soy phytoestrogens after BRCA2 knockdown by TaqMan Low-Density Array (TLDA). J Mol Signal,2009.4:p.3.
74. Zhang, L., et al., Low-density Taqman miRNA array reveals miRNAs differentially expressed in prostatic stem cells and luminal cells. Prostate, 2010.70(3):p.297-304.
75. Chow, T.F., et al., Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. Clin Biochem, 2010.43(1-2):p.150-8.
76. Zhang, Q., et al., [Profiling of microRNAs in mouse brain with real-time PCR array]. Beijing Da Xue Xue Bao,2009.41(2):p.152-7.
77. Resnick, K.E., et al., The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol,2009.112(1):p.55-9.
78. Lao, K., et al., Multiplexing RT-PCR for the detection of multiple miRNA species in small samples. Biochem Biophys Res Commun,2006.343(1):p. 85-9.
79. Anglicheau, D., et al., MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci U S A,2009.106(13):p.5330-5.
80. Bravo, V., et al., Instability of miRNA and cDNAs derivatives in RNA preparations. Biochem Biophys Res Commun,2007.353(4):p.1052-5.
81. Cheng, Y., et al., A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond),2010.
82. Chan, R.W., et al., Aberrant concentrations of liver-derived plasma albumin mRNA in liver pathologies. Clin Chem,2010.56(1):p.82-9.
83. Berezikov, E., et al., Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis. Genome Res,2006. 16(10):p.1289-98.
84. Adachi, T., et al., Plasma MicroRNA 499 as a Biomarker of Acute Myocardial Infarction. Clin Chem,2010.
85. Bustin, S.A. and R. Mueller, Real-time reverse transcription PCR (qRT-PCR) and its potential use in clinical diagnosis. Clin Sci (Lond),2005.109(4):p. 365-79.
86. Schetter, A.J. and C.C. Harris, Plasma microRNAs:a potential biomarker for colorectal cancer? Gut,2009.58(10):p.1318-9.
87. Markham, D.W. and J.A. Hill, MicroRNAs and heart failure diagnosis: MiR-acle or MiR-age? Circ Res,2010.106(6):p.1011-3.
88. Hausser, J., et al., MirZ:an integrated microRNA expression atlas and target prediction resource. Nucleic Acids Res,2009.37(Web Server issue):p. W266-72.
89. Vasiliou, V., K. Vasiliou, and D.W. Nebert, Human ATP-binding cassette (ABC) transporter family. Hum Genomics,2009.3(3):p.281-90.
90. Oram, J.F. and R.M. Lawn, ABCA1. The gatekeeper for eliminating excess tissue cholesterol. J Lipid Res,2001.42(8):p.1173-9.
91. Catalano, G., et al., Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects. J Lipid Res,2008.49(3):p.635-43.
92. Ma, K.L., et al., Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology, 2008.48(3):p.770-81.
93. Yancey, P.G., et al., SR-BI-and ABCA1-mediated cholesterol efflux to serum from patients with Alagille syndrome. J Lipid Res,2004.45(9):p. 1724-32.
94. Attia, N., et al., Impact of android overweight or obesity and insulin resistance on basal and postprandial SR-BI and ABCA1-mediated serum cholesterol efflux capacities. Atherosclerosis,2010.209(2):p.422-9.
1. Kruglyak, L. and D.A. Nickerson, Variation is the spice of life. Nat Genet, 2001.27(3):p.234-6.
2. Mattick, J.S., The functional genomics of noncoding RNA. Science,2005. 309(5740):p.1527-8.
3. Hannon, G.J., et al., The expanding universe of noncoding RNAs. Cold Spring Harb Symp Quant Biol,2006.71:p.551-64.
4. Chu, C.Y. and T.M. Rana, Small RNAs:regulators and guardians of the genome. J Cell Physiol,2007.213(2):p.412-9.
5. Lau, N.C., et al., An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science,2001.294(5543):p.858-62.
6. Lagos-Quintana, M., et al., Identification of novel genes coding for small expressed RNAs. Science,2001.294(5543):p.853-8.
7. Eddy, S.R., Non-coding RNA genes and the modern RNA world. Nat Rev Genet,2001.2(12):p.919-29.
8. Zamore, P.D. and B. Haley, Ribo-gnome:the big world of small RNAs. Science,2005.309(5740):p.1519-24.
9. Michalak, P., RNA world-the dark matter of evolutionary genomics. J Evol Biol,2006.19(6):p.1768-74.
10. Ghildiyal, M. and P.D. Zamore, Small silencing RNAs:an expanding universe. Nat Rev Genet,2009.10(2):p.94-108.
11. Grimm, D., Small silencing RNAs:state-of-the-art. Adv Drug Deliv Rev, 2009.61(9):p.672-703.
12. Storz, G., An expanding universe of noncoding RNAs. Science,2002. 296(5571):p.1260-3.
13. Nelson, P., et al., The microRNA world:small is mighty. Trends Biochem Sci,2003.28(10):p.534-40.
14.编者按.RNA组学：后基因组时代的科学前沿.中国科学C辑：生命科学,2009.39(1)：p.1-2.
15. Lee R C, F.R.L., Ambros, V., The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell,1993. 75:p.843-854.
16. Ambros, V., The functions of animal microRNAs. Nature,2004.431(7006): p.350-5.
17. Bartel, D.P., MicroRNAs:genomics, biogenesis, mechanism, and function. Cell,2004.116(2):p.281-97.
18. Farh, K.K., et al., The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science,2005.310(5755):p.1817-21.
19. Zhang, J., et al., Patterns of microRNA expression characterize stages of human B-cell differentiation. Blood,2009.113(19):p.4586-94.
20. Kosaka, N., et al., Identification of erythropoietin-induced microRNAs in haematopoietic cells during erythroid differentiation. Br J Haematol,2008. 142(2):p.293-300.
21. Chen, J.F., et al., The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet,2006.38(2):p.228-33.
22. Guo, C.J., et al., miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell:An essential role for apoptosis. J Hepatol,2009.50(4): p.766-78.
23. Witwer, K.W., et al., MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. J Immunol, 2010.184(5):p.2369-76.
24. Cordes, K.R., D. Srivastava, and K.N. Ivey, MicroRNAs in cardiac development. Pediatr Cardiol,2010.31(3):p.349-56.
25. Wang, D.Z., MicroRNAs in cardiac development and remodeling. Pediatr Cardiol,2010.31(3):p.357-62.
26. Daubman, S., MicroRNAs in angiogenesis and vascular smooth muscle cell function. Circ Res,2010.106(3):p.423-5.
27. Scalbert, E. and A. Bril, Implication of microRNAs in the cardiovascular system. Curr Opin Pharmacol,2008.8(2):p.181-8.
28. Vickers, K.C. and A.T. Remaley, MicroRNAs in atherosclerosis and lipoprotein metabolism. Curr Opin Endocrinol Diabetes Obes,2010.17(2): p.150-5.
29. Karp, X. and V. Ambros, Developmental biology. Encountering microRNAs in cell fate signaling. Science,2005.310(5752):p.1288-9.
30. Couzin, J., Genetics. Erasing microRNAs reveals their powerful punch. Science,2007.316(5824):p.530.
31. Leung, A.K. and P.A. Sharp, microRNAs:a safeguard against turmoil? Cell, 2007.130(4):p.581-5.
32. Couzin, J., MicroRNAs make big impression in disease after disease. Science,2008.319(5871):p.1782-4.
33. Kim, V.N., J. Han, and M.C. Siomi, Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol,2009.10(2):p.126-39.
34.陈芳,殷勤伟.调控基因表达的miRNA.科学通报,2005.50(13)：p. 1289-1299.
35. Baek, D., et al., The impact of microRNAs on protein output. Nature,2008. 455(7209):p.64-71.
36. Bartels, C.L. and G.J. Tsongalis, MicroRNAs:novel biomarkers for human cancer. Clin Chem,2009.55(4):p.623-31.
37. Morozova O, M.M., Applications of next-generation sequencing technologies in functional genomics. Genomics,2008.92(5):p.10.
38. Kuchenbauer, F., et al., In-depth characterization of the microRNA transcriptome in a leukemia progression model. Genome Res,2008.18(11): p.1787-97.
39. Jeffrey, S.S., Cancer biomarker profiling with microRNAs. Nat Biotechnol, 2008.26(4):p.400-1.
40. Ambros, V., et al., A uniform system for microRNA annotation. RNA,2003. 9(3):p.277-9.
41. Saito, T. and P. Saetrom, MicroRNAs-targeting and target prediction. N Biotechnol,2010.
42. Turner, M. and E. Vigorito, Regulation of B-and T-cell differentiation by a single microRNA. Biochem Soc Trans,2008.36(Pt 3):p.531-3.
43. Wang, M., et al., miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression. J Pathol,2008.215(1):p.13-20.
44. Su, H., et al., MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res,2009.69(3): p.1135-42.
45. Strum, J.C., et al., MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirTl. Mol Endocrinol,2009. 23(11):p.1876-84.
46. Weidhaas, J., Using microRNAs to understand cancer biology. Lancet Oncol, 2010.11(2):p.106-7.
47. Davalos, V. and M. Esteller, MicroRNAs and cancer epigenetics:a macrorevolution. Curr Opin Oncol,2010.22(1):p.35-45.
48. O'Connell, R.M., et al., Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol,2010.10(2):p.111-22.
49. Davidson-Moncada, J., F.N. Papavasiliou, and W. Tam, MicroRNAs of the immune system:roles in inflammation and cancer. Ann N Y Acad Sci,2010. 1183:p.183-94.
50. Lau, P. and B. de Strooper, Dysregulated microRNAs in neurodegenerative disorders. Semin Cell Dev Biol,2010.
51. Condorelli, G., M.V. Latronico, and G.W. Dorn,2nd, microRNAs in heart disease:putative novel therapeutic targets? Eur Heart J,2010.31(6):p. 649-58.
52. Small, E.M., R.J. Frost, and E.N. Olson, MicroRNAs add a new dimension to cardiovascular disease. Circulation,2010.121(8):p.1022-32.
53. Cai, B., Z. Pan, and Y. Lu, The Roles of MicroRNAs in Heart Diseases:A Novel Important Regulator. Curr Med Chem,2010.17(5):p.407-11.
54. Li, S., et al., Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J Lipid Res,2009.50(9):p.1756-65.
55. Anglicheau, D., et al., MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci U S A,2009.106(13):p.5330-5.
56. Manikandan, J., et al., Oncomirs:The potential role of non-coding microRNAs in understanding cancer. Bioinformation,2008.2(8):p.330-4.
57. Cho, W.C., MicroRNAs in cancer-from research to therapy. Biochim Biophys Acta,2010.1805(2):p.209-217.
58. Kusenda, B., et al., MicroRNA biogenesis, functionality and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2006.150(2):p.205-15.
59. Paranjape, T., F.J. Slack, and J.B. Weidhaas, MicroRNAs:tools for cancer diagnostics. Gut,2009.58(11):p.1546-54.
60. Calin, G.A. and C.M. Croce, MicroRNA signatures in human cancers. Nat Rev Cancer,2006.6(11):p.857-66.
61. McCarthy, N., Cancer:Small losses, big gains with microRNAs. Nat Rev Genet,2010.11(1):p.8.
62. Zhang, L., et al., microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A,2006.103(24):p.9136-41.
63. Calin, G.A., et al., Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A,2002.99(24):p.15524-9.
64. Santarpia, L., M. Nicoloso, and G.A. Calin, MicroRNAs:a complex regulatory network drives the acquisition of malignant cell phenotype. Endocr Relat Cancer,2010.17(1):p. F51-75.
65. Lin, C.J., et al., miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines. Biochem Biophys Res Commun,2008. 375(3):p.315-20.
66. Lin, S.L., et al., Loss of mir-146a function in hormone-refractory prostate cancer. RNA,2008.14(3):p.417-24.
67. Ventura, A. and T. Jacks, MicroRNAs and cancer:short RNAs go a long way. Cell,2009.136(4):p.586-91.
68. Xu, B., et al., A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate,2010.70(5):p.467-72.
69. Hu, Z., et al., Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest,2008.118(7):p.2600-8.
70. Zhu, Z., et al., Genetic variation of miRNA sequence in pancreatic cancer. Acta Biochim Biophys Sin (Shanghai),2009.41(5):p.407-13.
71. Giannakakis, A., et al., miRNA genetic alterations in human cancers. Expert Opin Biol Ther,2007.7(9):p.1375-86.
72. Yang, J., et al., Analysis of sequence variations in 59 microRNAs in hepatocellular carcinomas. Mutat Res,2008.638(1-2):p.205-9.
73. Calin, G.A. and C.M. Croce, MicroRNA-cancer connection:the beginning of a new tale. Cancer Res,2006.66(15):p.7390-4.
74. Gregory, R.I. and R. Shiekhattar, MicroRNA biogenesis and cancer. Cancer Res,2005.65(9):p.3509-12.
75. Ferdin, J., T. Kunej, and G.A. Calin, Non-coding RNAs:identification of cancer-associated microRNAs by gene profiling. Technol Cancer Res Treat, 2010.9(2):p.123-38.
76. Du, L. and A. Pertsemlidis, microRNAs and lung cancer:tumors and 22-mers. Cancer Metastasis Rev,2010.29(1):p.109-22.
77. Oulas, A., M. Reczko, and P. Poirazi, MicroRNAs and cancer-the search begins! IEEE Trans Inf Technol Biomed,2009.13(1):p.67-77.
78. Yanaihara, N., et al., Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell,2006.9(3):p.189-98.
79. Calin, GA., et al., MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A,2004.101(32):p. 11755-60.
80. Lu, J., et al., MicroRNA expression profiles classify human cancers. Nature, 2005.435(7043):p.834-8.
81. Rosenfeld, N., et al., MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol,2008.26(4):p.462-9.
82. Li, W., et al., Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer,2008.123(7):p.1616-22.
83. Guo, Y., et al., Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res,2008.68(1):p.26-33.
84. Varnholt, H., et al., MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology,2008.47(4):p. 1223-32.
85. Jiang, J., et al., Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res,2008.14(2):p.419-27.
86. Budhu, A., et al., Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology,2008.47(3):p.897-907.
87. Kutay, H., et al., Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem,2006.99(3):p.671-8.
88. Gregory, R.I., et al., The Microprocessor complex mediates the genesis of microRNAs. Nature,2004.432(7014):p.235-40.
89. Tricoli, J.V. and J.W. Jacobson, MicroRNA:Potential for Cancer Detection, Diagnosis, and Prognosis. Cancer Res,2007.67(10):p.4553-5.
90. Lawrie, C.H., et al., Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol,2008.141(5):p.672-5.
91. Mitchell, P.S., et al., Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A,2008.105(30):p.10513-8.
92. Chen, X., et al., Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res,2008. 18(10):p.997-1006.
93. Ng, E.K., et al., Differential expression of microRNAs in plasma of patients with colorectal cancer:a potential marker for colorectal cancer screening. Gut,2009.58(10):p.1375-81.
94. Huang, Z., et al., Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer,2009.
95. Resnick, K.E., et al., The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol,2009.112(1):p.55-9.
96. Heneghan, H.M., et al., Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg,2010.251(3):p.499-505.
97. Wang, K., et al., Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A,2009.106(11):p. 4402-7.
98. Wang, G.K., et al., Eur Heart J,2010.31 (6):p.659-66.
99. Tijsen, A.J., et al., MiR423-5p As a Circulating Biomarker for Heart Failure. Circ Res,2010.
100. Wang, J.F., et al., Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun,2010.
101. Ai, J., et al., Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun,2010.391(1): p.73-7.
102. Cheng, Y., et al., A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond),2010.
103. Tsujiura, M., et al., Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer,2010.
104. Wang, J., et al., MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila Pa),2009.2(9):p.807-13.
105. Hu, Z., et al., Serum MicroRNA Signatures Identified in a Genome-Wide Serum MicroRNA Expression Profiling Predict Survival of Non-Small-Cell Lung Cancer. J Clin Oncol,2010.
106. Ji, X., et al., Plasma miR-208 as a biomarker of myocardial injury. Clin Chem,2009.55(11):p.1944-9.
107. Vlassov, V.V., P.P. Laktionov, and E.Y. Rykova, Circulating Nucleic Acids as a Potential Source for Cancer Biomarkers. Curr Mol Med,2010.
108. Chin, L.J. and F.J. Slack, A truth serum for cancer-microRNAs have major potential as cancer biomarkers. Cell Res,2008.18(10):p.983-4.
109. Rosell, R., J. Wei, and M. Taron, Circulating MicroRNA Signatures of Tumor-Derived Exosomes for Early Diagnosis of Non-Small-Cell Lung Cancer. Clin Lung Cancer,2009.10(1):p.8-9.
110. van Niel, G., et al., Exosomes:a common pathway for a specialized function. J Biochem,2006.140(1):p.13-21.
111. Valadi, H., et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol,2007. 9(6):p.654-9.
112. Liu, C.J., et al., Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis,2010.
113. Michael, A., et al., Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis,2010.16(1):p.34-8.
114. Park, N.J., et al., Salivary microRNA:discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res,2009.15(17):p. 5473-7.
115. Gilad, S., et al., Serum microRNAs are promising novel biomarkers. PLoS One,2008.3(9):p. e3148.
116. Chim, S.S., et al., Detection and characterization of placental microRNAs in maternal plasma. Clin Chem,2008.54(3):p.482-90.
117. Laterza, O.F., et al., Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury. Clin Chem,2009.55(11):p.1977-83.
118. Wang, GK., et al., Circulating microRNA:a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J,2010. 31(6):p.659-66.
119. Hunter, M.P., et al., Detection of microRNA expression in human peripheral blood microvesicles. PLoS One,2008.3(11):p. e3694.
120. Rabinowits, G., et al., Exosomal microRNA:a diagnostic marker for lung cancer. Clin Lung Cancer,2009.10(1):p.42-6.
121. Simpson, R.J., et al., Exosomes:proteomic insights and diagnostic potential. Expert Rev Proteomics,2009.6(3):p.267-83.
122. Taylor, D.D. and C. Gercel-Taylor, MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol,2008. 110(1):p.13-21.
123.景花,宋沁馨,周国华.MicroRNA定量检测方法的研究进展.遗传,2010.32(1)：p.31-40.
124. Liu, C.G., et al., MicroRNA expression profiling using microarrays. Nat Protoc,2008.3(4):p.563-78.
125. Liu, C.G., et al., Expression profiling of microRNA using oligo DNA arrays. Methods,2008.44(1):p.22-30.
126. Lodes, M.J., et al., Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One,2009.4(7):p. e6229.
127. Lao, K., et al., Multiplexing RT-PCR for the detection of multiple miRNA species in small samples. Biochem Biophys Res Commun,2006.343(1):p. 85-9.
128. Tang, F., et al.,220-plex microRNA expression profile of a single cell. Nat Protoc,2006.1(3):p.1154-9.
129.王芳,余佳,张俊武.小RNA(MicroRNA)研究方法.中国生物化学与分子生物学报,2006.22(10)：p.772-779.
130.滕晓坤,肖华胜.基因芯片与高通量DNA测序技术前景分析.中国科学C辑：生命科学,2008.38(10)：p.891-899.
131. Cho, W.C., MicroRNAs:Potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol,2009.
132. Cortez, M.A. and GA. Calin, MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther,2009. 9(6):p.703-711.
133. Vlassov, V.V., P.P. Laktionov, and E.Y. Rykova, Circulating nucleic acids as a potential source for cancer biomarkers. Curr Mol Med,2010.10(2):p. 142-65.
134. Chan, K.C. and Y.M. Lo, Circulating tumour-derived nucleic acids in cancer patients:potential applications as tumour markers. Br J Cancer,2007.96(5): p.681-5.
[1]Fang Y, Shang QL, Liu JY, Li D, Xu WZ, Teng X, et al. Prevalence of occult hepatitis B virus infection among hepatopathy patients and healthy people in China. J Infect 2009;58(5):383-388.
[2]Zhou H, Wang H, Zhou D, Wang Q, Zou S, Tu Q, et al. Hepatitis B virus-associated intrahepatic cholangiocarcinoma and hepatocellular carcinoma may hold common disease process for carcinogenesis.[Epub ahead of print] Eur J Cancer March 8,2010 as doi:10.1016/j.ejca.2010.02.005.
[3]Aravalli RN, Steer CJ, Cressman EK. Molecular Mechanisms of Hepatocellular Carcinoma. Hepatology 2008;48(6):2047-2063.
[4]Thorgeirsson SS, Lee J-S, Grisham JW. Functional Genomics of Hepatocellular Carcinoma. Hepatology 2006;43(2) Suppl:S145-150.
[5]Bartel DP. MicroRNAs:target recognition and regulatory functions. Cell 2009; 136(2):215-233.
[6]Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature 2005;435(7043):834-838.
[7]Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008; 299(4):425-436.
[8]Anglicheau D, Sharma VK, Ding R, Hummel A, Snopkowski C, Dadhania D, et al. MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci USA 2009; 106(13):5330-5335.
[9]Li S, Chen X, Zhang H, Liang X, Xiang Y, Yu C, et al. Differential Expression of MicroRNAs in Mouse Liver under Aberrant Energy Metabolic Status. J Lipid Res 2009;50(9):1756-1765.
[10]Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105(30):10513-10518.
[11]Chen Xi, Ba Yi, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008;18(10):997-1006.
[12]Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 2009;112:55-59.
[13]Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 2008; 141:672-674.
[14]Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, et al. Differential expression of microRNAs in plasma of colorectal cancer patients:A potential marker for colorectal cancer screening. Gut 2009;58:1375-1381.
[15]Ai J, Zhang R, Li Y, Pu J, Lu Y, Jiao J, et al. Circulating microRNA-1 as a potential novel biomarkers for acute myocardial infarction. Biochem Biophys Res Commun 2010;391(1):73-77.
[16]Ji X, Takahashi R, Hiura Y, Hirokawa G, Fukushima Y, Iwai N. Plasma miR-208 as a Biomarker of Myocardial Injury. Clin Chem 2009;55(11):1944-1949.
[17]Li W, Xie L, He X, Li J, Tu K, Wei L, et al. Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer 2008; 123(7): 1616-1622.
[18]Ladeiro Y, Couchy G, Balabaud C, Bioulac-Sage P, Pelletier L, Rebouissou S, et al. MicroRNA Profiling in Hepatocellular Tumors Is Associated with Clinical Features and Oncogene/Tumor Suppressor Gene Mutations. Hepatology 2008;47(6): 1955-1963.
[19]Connolly E, Melegari M, Landgraf P, Tchaikovskaya T, Tennant BC, Slagle BL, et al. Elevated Expression of the miR-17-92 Polycistron and miR-21 in Hepadnavirus-Associated Hepatocellular Carcinoma Contributes to the Malignant Phenotype. Am J Pathol 2008; 173(3):856-864.
[20]Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 2006;25(17):2537-2545.
[21]Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu Z, et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 2009; 106(11):4402-4407.
[22]Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protocols 2008;3(6):1101-1108.
[23]Livak KJ, Schmittgent TD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and 2-ΔΔCT Method. Mehtods 2001;25:402-408.
[24]Zhu W, Qin W, Atasoy U, Sauter ER. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes 2009;2:89.
[25]Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, et al. MicroRNAs in Plasma of Pancreatic Ductal Adenocarcinoma Patients as Novel Blood-Based Biomarkers of Disease. Cancer Prev Res 2009;2(9):807-813.
[26]Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, et al. Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PloS ONE 2009;4(5):e5532.
[27]Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 2010;251(3):499-505.
[28]Sakamoto M, Mori T, Masugi Y, Effendi K, Rie I, Du W. Candidate molecular markers for histological diagnosis of early hepatocellular carcinoma. Intervirology 2008;51(S1):42-45.
[29]Tang F, Hajkova P, Barton SC, O'Carroll D, Lee C, Lao K, et al.220-plex microRNA expression profile of a single cell. Nat Protocols 2006; 1(3):1154-1159.
[30]Mestdagh P, Feys T, Bernard N, Guenther S, Chen C, Speleman F, et al. High-throughput stem-loop RT-qPCR miRNA expression profiling using minute amounts of input RNA. Nucl Acids Res 2008;36(21):e143.
[31]Hu Zh, Chen X, Zhao Y, Tian T, Jin G, Shu Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol [Epub ahead of print],2010 as doi:10.1200/JCO.2009.24.9342.
[1]刘永学,高月.应激研究进展.中国病理生理杂志,2002,18(2)；218-.
[2]Clark VR, Moore CL, Adams JH. Cholesterol concentrations and cardiovascular reactivity to stress in African American college volunteers. J Behav Med,1998,21(5):505-
[3]McCann BS, Benjamin GA,Wilkinson CW, et al. Plasma lipid concentrations during episodic occupational stress. Ann Behav Med,1999,21 (2):103-.
[4]Grundy S, Griffin A.C. Effects of Periodic Mental Stress on Serum Cholesterol Levels. Circulation,1959,19;496-.
[5]Siegrist J, Peter R, Cremer P, et al. Chronic work stress is associated with atherogenic lipids and elevated fibrinogen in middle aged men. J Intern Med, 1997,242(2):149-.
[6]Bachen EA, Muldoon MF, Matthews KA, et al. Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress. Psychosom Med,2002,64(4):587-
2. Bird, C.P., B.E. Stranger, and E.T. Dermitzakis, Functional variation and evolution of non-coding DNA. Curr Opin Genet Dev,2006.16(6):p. 559-64.
3. Subirana, J.A. and X. Messeguer, The most frequent short sequences in non-coding DNA. Nucleic Acids Res,2010.38(4):p.1172-81.
4. Kurth, H.M. and K. Mochizuki, Non-coding RNA:a bridge between small RNA and DNA. RNA Biol,2009.6(2):p.138-40.
5. Micro RNA and non-coding DNA and repeats. Genomic Med,2008.2(3-4): p.205-7.
6. Mattick, J.S. and I.V. Makunin, Non-coding RNA. Hum Mol Genet,2006. 15 Spec No 1:p.R 17-29.
7. Nelson, P., et al., The microRNA world:small is mighty. Trends Biochem Sci,2003.28(10):p.534-40.
8. Eddy, S.R., Non-coding RNA genes and the modern RNA world. Nat Rev Genet,2001.2(12):p.919-29.
9. Bartel, D.P., MicroRNAs:genomics, biogenesis, mechanism, and function. Cell,2004.116(2):p.281-97.
10. O'Hara, S.P., et al., MicroRNAs:key modulators of posttranscriptional gene expression. Gastroenterology,2009.136(1):p.17-25.
11. Bartel, D.P., MicroRNAs:target recognition and regulatory functions. Cell, 2009.136(2):p.215-33.
12. Leung, A.K. and P.A. Sharp, microRNAs:a safeguard against turmoil? Cell, 2007.130(4):p.581-5.
13. Ferdin, J., T. Kunej, and G.A. Calin, Non-coding RNAs:identification of cancer-associated microRNAs by gene profiling. Technol Cancer Res Treat, 2010.9(2):p.123-38.
14. Paranjape, T., F.J. Slack, and J.B. Weidhaas, MicroRNAs:tools for cancer diagnostics. Gut,2009.58(11):p.1546-54.
15. Cho, W.C., MicroRNAs in cancer-from research to therapy. Biochim Biophys Acta,2010.1805(2):p.209-217.
16. Oulas, A., M. Reczko, and P. Poirazi, MicroRNAs and cancer-the search begins! IEEE Trans Inf Technol Biomed,2009.13(1):p.67-77.
17. O'Connell, R.M., et al., Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol,2010.10(2):p.111-22.
18. Harris, A., S.M. Krams, and O.M. Martinez, MicroRNAs as Immune Regulators:Implications for Transplantation. Am J Transplant,2010.
19. Lau, P. and B. de Strooper, Dysregulated microRNAs in neurodegenerative disorders. Semin Cell Dev Biol,2010.
20. Scalbert, E. and A. Bril, Implication of microRNAs in the cardiovascular system. Curr Opin Pharmacol,2008.8(2):p.181-8.
21. Small, E.M., R.J. Frost, and E.N. Olson, MicroRNAs add a new dimension to cardiovascular disease. Circulation,2010.121(8):p.1022-32.
22. Li, S., et al., Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J Lipid Res,2009.50(9):p.1756-65.
23. Jeffrey, S.S., Cancer biomarker profiling with microRNAs. Nat Biotechnol, 2008.26(4):p.400-1.
24. Lu, J., et al., MicroRNA expression profiles classify human cancers. Nature, 2005.435(7043):p.834-8.
25. Iorio, M.V., et al., MicroRNA gene expression deregulation in human breast cancer. Cancer Res,2005.65(16):p.7065-70.
26. Rosenfeld, N., et al., MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol,2008.26(4):p.462-9.
27. Voorhoeve, P.M., MicroRNAs:Oncogenes, tumor suppressors or master regulators of cancer heterogeneity? Biochim Biophys Acta,2010.1805(1):p. 72-86.
28. Couzin, J., MicroRNAs make big impression in disease after disease. Science,2008.319(5871):p.1782-4.
29. Lawrie, C.H., et al., Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol,2008.141(5):p.672-5.
30. Mitchell, P.S., et al., Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A,2008.105(30):p.10513-8.
31. Chen, X., et al., Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res,2008. 18(10):p.997-1006.
32. Ng, E.K., et al., Differential expression of microRNAs in plasma of patients with colorectal cancer:a potential marker for colorectal cancer screening. Gut,2009.58(10):p.1375-81.
33. Huang, Z., et al., Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer,2009.
34. Heneghan, H.M., et al., Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg,2010.251(3):p.499-505.
35. Zhu, W., et al., Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes,2009.2:p.89.
36. Heneghan, H.M., et al., MicroRNAs as Novel Biomarkers for Breast Cancer. J Oncol,2009.2009:p.950201.
37. Tsujiura, M., et al., Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer,2010.
38. Ji, X., et al., Plasma miR-208 as a biomarker of myocardial injury. Clin Chem,2009.55(11):p.1944-9.
39. Ai, J., et al., Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun,2010.391(1): p.73-7.
40. Tijsen, A.J., et al., MiR423-5p As a Circulating Biomarker for Heart Failure. Circ Res,2010.
41. Wang, K., et al., Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A,2009.106(11):p. 4402-7.
42.慢性乙型肝炎抗病毒治疗专家委员会.慢性乙型肝炎抗病毒治疗专家共识.中华实验和临床感染病杂志.2010.4(1)：p.82-91.
43. Tan, L.P., et al., miRNA profiling of B-cell subsets:specific miRNA profile for germinal center B cells with variation between centroblasts and centrocytes. Lab Invest,2009.89(6):p.708-16.
44. Zhang, J., et al., Patterns of microRNA expression characterize stages of human B-cell differentiation. Blood,2009.113(19):p.4586-94.
45. Bartels, C.L. and G.J. Tsongalis, MicroRNAs:novel biomarkers for human cancer. Clin Chem,2009.55(4):p.623-31.
46. El-Hefnawy, T., et al., Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics. Clin Chem,2004. 50(3):p.564-73.
47. Wang, J., et al., MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila Pa),2009.2(9):p.807-13.
48. Gilad, S., et al., Serum microRNAs are promising novel biomarkers. PLoS One,2008.3(9):p. e3148.
49. Jung, M., et al., Robust MicroRNA Stability in Degraded RNA Preparations from Human Tissue and Cell Samples. Clin Chem,2010.
50. Li, J., et al., Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells. BMC Biotechnol,2007.7:p.36.
51. Wang, G.K., et al., Circulating microRNA:a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J,2010. 31(6):p.659-66.
52. Cheng, Y., et al., A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond),2010.119(2):p.87-95.
53. Valadi, H., et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol,2007. 9(6):p.654-9.
54. Taylor, D.D. and C. Gercel-Taylor, MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol,2008. 110(1):p.13-21.
55. van Niel, G., et al., Exosomes:a common pathway for a specialized function. J Biochem,2006.140(1):p.13-21.
56. Simpson, R.J., et al., Exosomes:proteomic insights and diagnostic potential. Expert Rev Proteomics,2009.6(3):p.267-83.
57. Chen, C., et al., Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res,2005.33(20):p. e179.
58. Shingara, J., et al., An optimized isolation and labeling platform for accurate microRNA expression profiling. RNA,2005.11(9):p.1461-70.
59. Liu, C.G., et al., MicroRNA expression profiling using microarrays. Nat Protoc,2008.3(4):p.563-78.
60. Yin, J.Q., R.C. Zhao, and K.V. Morris, Profiling microRNA expression with microarrays. Trends Biotechnol,2008.26(2):p.70-6.
61. Huang, X.H., et al., Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma:miR-338 is downregulated. Hepatol Res,2009.39(8):p.786-94.
62. Hu, Z., et al., Serum MicroRNA Signatures Identified in a Genome-Wide Serum MicroRNA Expression Profiling Predict Survival of Non-Small-Cell Lung Cancer. J Clin Oncol,2010.
63. Tang, F., et al.,220-plex microRNA expression profile of a single cell. Nat Protoc,2006.1(3):p.1154-9.
64. Wang, X., A PCR-based platform for microRNA expression profiling studies. RNA,2009.15(4):p.716-23.
65.徐洁等.肝脏特异性miR-122的分子生物学特性及功能.生物物理学报,2009.25(3)：p.183-191.
66. Esau, C., et al., miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab,2006.3(2):p.87-98.
67. Su, H., et al., MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res,2009.69(3): p.1135-42.
68. Murakami, Y., et al., Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene, 2006.25(17):p.2537-45.
69. Schmittgen, T.D. and K..J. Livak, Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc,2008.3(6):p.1101-8.
70. Sato, F., et al., Intra-platform repeatability and inter-platform comparability of microRNA microarray technology. PLoS One,2009.4(5):p. e5540.
71. Cortez, M.A. and G.A. Calin, MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther,2009. 9(6):p.703-711.
72. Lu, B., et al., TaqMan low density array is roughly right for gene expression quantification in colorectal cancer. Clin Chim Acta,2008.389(1-2):p. 146-51.
73. Satih, S., et al., Expression analyses of nuclear receptor genes in breast cancer cell lines exposed to soy phytoestrogens after BRCA2 knockdown by TaqMan Low-Density Array (TLDA). J Mol Signal,2009.4:p.3.
74. Zhang, L., et al., Low-density Taqman miRNA array reveals miRNAs differentially expressed in prostatic stem cells and luminal cells. Prostate, 2010.70(3):p.297-304.
75. Chow, T.F., et al., Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. Clin Biochem, 2010.43(1-2):p.150-8.
76. Zhang, Q., et al., [Profiling of microRNAs in mouse brain with real-time PCR array]. Beijing Da Xue Xue Bao,2009.41(2):p.152-7.
77. Resnick, K.E., et al., The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol,2009.112(1):p.55-9.
78. Lao, K., et al., Multiplexing RT-PCR for the detection of multiple miRNA species in small samples. Biochem Biophys Res Commun,2006.343(1):p. 85-9.
79. Anglicheau, D., et al., MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci U S A,2009.106(13):p.5330-5.
80. Bravo, V., et al., Instability of miRNA and cDNAs derivatives in RNA preparations. Biochem Biophys Res Commun,2007.353(4):p.1052-5.
81. Cheng, Y., et al., A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond),2010.
82. Chan, R.W., et al., Aberrant concentrations of liver-derived plasma albumin mRNA in liver pathologies. Clin Chem,2010.56(1):p.82-9.
83. Berezikov, E., et al., Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis. Genome Res,2006. 16(10):p.1289-98.
84. Adachi, T., et al., Plasma MicroRNA 499 as a Biomarker of Acute Myocardial Infarction. Clin Chem,2010.
85. Bustin, S.A. and R. Mueller, Real-time reverse transcription PCR (qRT-PCR) and its potential use in clinical diagnosis. Clin Sci (Lond),2005.109(4):p. 365-79.
86. Schetter, A.J. and C.C. Harris, Plasma microRNAs:a potential biomarker for colorectal cancer? Gut,2009.58(10):p.1318-9.
87. Markham, D.W. and J.A. Hill, MicroRNAs and heart failure diagnosis: MiR-acle or MiR-age? Circ Res,2010.106(6):p.1011-3.
88. Hausser, J., et al., MirZ:an integrated microRNA expression atlas and target prediction resource. Nucleic Acids Res,2009.37(Web Server issue):p. W266-72.
89. Vasiliou, V., K. Vasiliou, and D.W. Nebert, Human ATP-binding cassette (ABC) transporter family. Hum Genomics,2009.3(3):p.281-90.
90. Oram, J.F. and R.M. Lawn, ABCA1. The gatekeeper for eliminating excess tissue cholesterol. J Lipid Res,2001.42(8):p.1173-9.
91. Catalano, G., et al., Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects. J Lipid Res,2008.49(3):p.635-43.
92. Ma, K.L., et al., Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice. Hepatology, 2008.48(3):p.770-81.
93. Yancey, P.G., et al., SR-BI-and ABCA1-mediated cholesterol efflux to serum from patients with Alagille syndrome. J Lipid Res,2004.45(9):p. 1724-32.
94. Attia, N., et al., Impact of android overweight or obesity and insulin resistance on basal and postprandial SR-BI and ABCA1-mediated serum cholesterol efflux capacities. Atherosclerosis,2010.209(2):p.422-9.
1. Kruglyak, L. and D.A. Nickerson, Variation is the spice of life. Nat Genet, 2001.27(3):p.234-6.
2. Mattick, J.S., The functional genomics of noncoding RNA. Science,2005. 309(5740):p.1527-8.
3. Hannon, G.J., et al., The expanding universe of noncoding RNAs. Cold Spring Harb Symp Quant Biol,2006.71:p.551-64.
4. Chu, C.Y. and T.M. Rana, Small RNAs:regulators and guardians of the genome. J Cell Physiol,2007.213(2):p.412-9.
5. Lau, N.C., et al., An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science,2001.294(5543):p.858-62.
6. Lagos-Quintana, M., et al., Identification of novel genes coding for small expressed RNAs. Science,2001.294(5543):p.853-8.
7. Eddy, S.R., Non-coding RNA genes and the modern RNA world. Nat Rev Genet,2001.2(12):p.919-29.
8. Zamore, P.D. and B. Haley, Ribo-gnome:the big world of small RNAs. Science,2005.309(5740):p.1519-24.
9. Michalak, P., RNA world-the dark matter of evolutionary genomics. J Evol Biol,2006.19(6):p.1768-74.
10. Ghildiyal, M. and P.D. Zamore, Small silencing RNAs:an expanding universe. Nat Rev Genet,2009.10(2):p.94-108.
11. Grimm, D., Small silencing RNAs:state-of-the-art. Adv Drug Deliv Rev, 2009.61(9):p.672-703.
12. Storz, G., An expanding universe of noncoding RNAs. Science,2002. 296(5571):p.1260-3.
13. Nelson, P., et al., The microRNA world:small is mighty. Trends Biochem Sci,2003.28(10):p.534-40.
14.编者按.RNA组学：后基因组时代的科学前沿.中国科学C辑：生命科学,2009.39(1)：p.1-2.
15. Lee R C, F.R.L., Ambros, V., The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell,1993. 75:p.843-854.
16. Ambros, V., The functions of animal microRNAs. Nature,2004.431(7006): p.350-5.
17. Bartel, D.P., MicroRNAs:genomics, biogenesis, mechanism, and function. Cell,2004.116(2):p.281-97.
18. Farh, K.K., et al., The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science,2005.310(5755):p.1817-21.
19. Zhang, J., et al., Patterns of microRNA expression characterize stages of human B-cell differentiation. Blood,2009.113(19):p.4586-94.
20. Kosaka, N., et al., Identification of erythropoietin-induced microRNAs in haematopoietic cells during erythroid differentiation. Br J Haematol,2008. 142(2):p.293-300.
21. Chen, J.F., et al., The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet,2006.38(2):p.228-33.
22. Guo, C.J., et al., miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell:An essential role for apoptosis. J Hepatol,2009.50(4): p.766-78.
23. Witwer, K.W., et al., MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. J Immunol, 2010.184(5):p.2369-76.
24. Cordes, K.R., D. Srivastava, and K.N. Ivey, MicroRNAs in cardiac development. Pediatr Cardiol,2010.31(3):p.349-56.
25. Wang, D.Z., MicroRNAs in cardiac development and remodeling. Pediatr Cardiol,2010.31(3):p.357-62.
26. Daubman, S., MicroRNAs in angiogenesis and vascular smooth muscle cell function. Circ Res,2010.106(3):p.423-5.
27. Scalbert, E. and A. Bril, Implication of microRNAs in the cardiovascular system. Curr Opin Pharmacol,2008.8(2):p.181-8.
28. Vickers, K.C. and A.T. Remaley, MicroRNAs in atherosclerosis and lipoprotein metabolism. Curr Opin Endocrinol Diabetes Obes,2010.17(2): p.150-5.
29. Karp, X. and V. Ambros, Developmental biology. Encountering microRNAs in cell fate signaling. Science,2005.310(5752):p.1288-9.
30. Couzin, J., Genetics. Erasing microRNAs reveals their powerful punch. Science,2007.316(5824):p.530.
31. Leung, A.K. and P.A. Sharp, microRNAs:a safeguard against turmoil? Cell, 2007.130(4):p.581-5.
32. Couzin, J., MicroRNAs make big impression in disease after disease. Science,2008.319(5871):p.1782-4.
33. Kim, V.N., J. Han, and M.C. Siomi, Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol,2009.10(2):p.126-39.
34.陈芳,殷勤伟.调控基因表达的miRNA.科学通报,2005.50(13)：p. 1289-1299.
35. Baek, D., et al., The impact of microRNAs on protein output. Nature,2008. 455(7209):p.64-71.
36. Bartels, C.L. and G.J. Tsongalis, MicroRNAs:novel biomarkers for human cancer. Clin Chem,2009.55(4):p.623-31.
37. Morozova O, M.M., Applications of next-generation sequencing technologies in functional genomics. Genomics,2008.92(5):p.10.
38. Kuchenbauer, F., et al., In-depth characterization of the microRNA transcriptome in a leukemia progression model. Genome Res,2008.18(11): p.1787-97.
39. Jeffrey, S.S., Cancer biomarker profiling with microRNAs. Nat Biotechnol, 2008.26(4):p.400-1.
40. Ambros, V., et al., A uniform system for microRNA annotation. RNA,2003. 9(3):p.277-9.
41. Saito, T. and P. Saetrom, MicroRNAs-targeting and target prediction. N Biotechnol,2010.
42. Turner, M. and E. Vigorito, Regulation of B-and T-cell differentiation by a single microRNA. Biochem Soc Trans,2008.36(Pt 3):p.531-3.
43. Wang, M., et al., miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression. J Pathol,2008.215(1):p.13-20.
44. Su, H., et al., MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res,2009.69(3): p.1135-42.
45. Strum, J.C., et al., MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirTl. Mol Endocrinol,2009. 23(11):p.1876-84.
46. Weidhaas, J., Using microRNAs to understand cancer biology. Lancet Oncol, 2010.11(2):p.106-7.
47. Davalos, V. and M. Esteller, MicroRNAs and cancer epigenetics:a macrorevolution. Curr Opin Oncol,2010.22(1):p.35-45.
48. O'Connell, R.M., et al., Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol,2010.10(2):p.111-22.
49. Davidson-Moncada, J., F.N. Papavasiliou, and W. Tam, MicroRNAs of the immune system:roles in inflammation and cancer. Ann N Y Acad Sci,2010. 1183:p.183-94.
50. Lau, P. and B. de Strooper, Dysregulated microRNAs in neurodegenerative disorders. Semin Cell Dev Biol,2010.
51. Condorelli, G., M.V. Latronico, and G.W. Dorn,2nd, microRNAs in heart disease:putative novel therapeutic targets? Eur Heart J,2010.31(6):p. 649-58.
52. Small, E.M., R.J. Frost, and E.N. Olson, MicroRNAs add a new dimension to cardiovascular disease. Circulation,2010.121(8):p.1022-32.
53. Cai, B., Z. Pan, and Y. Lu, The Roles of MicroRNAs in Heart Diseases:A Novel Important Regulator. Curr Med Chem,2010.17(5):p.407-11.
54. Li, S., et al., Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J Lipid Res,2009.50(9):p.1756-65.
55. Anglicheau, D., et al., MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci U S A,2009.106(13):p.5330-5.
56. Manikandan, J., et al., Oncomirs:The potential role of non-coding microRNAs in understanding cancer. Bioinformation,2008.2(8):p.330-4.
57. Cho, W.C., MicroRNAs in cancer-from research to therapy. Biochim Biophys Acta,2010.1805(2):p.209-217.
58. Kusenda, B., et al., MicroRNA biogenesis, functionality and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2006.150(2):p.205-15.
59. Paranjape, T., F.J. Slack, and J.B. Weidhaas, MicroRNAs:tools for cancer diagnostics. Gut,2009.58(11):p.1546-54.
60. Calin, G.A. and C.M. Croce, MicroRNA signatures in human cancers. Nat Rev Cancer,2006.6(11):p.857-66.
61. McCarthy, N., Cancer:Small losses, big gains with microRNAs. Nat Rev Genet,2010.11(1):p.8.
62. Zhang, L., et al., microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A,2006.103(24):p.9136-41.
63. Calin, G.A., et al., Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A,2002.99(24):p.15524-9.
64. Santarpia, L., M. Nicoloso, and G.A. Calin, MicroRNAs:a complex regulatory network drives the acquisition of malignant cell phenotype. Endocr Relat Cancer,2010.17(1):p. F51-75.
65. Lin, C.J., et al., miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines. Biochem Biophys Res Commun,2008. 375(3):p.315-20.
66. Lin, S.L., et al., Loss of mir-146a function in hormone-refractory prostate cancer. RNA,2008.14(3):p.417-24.
67. Ventura, A. and T. Jacks, MicroRNAs and cancer:short RNAs go a long way. Cell,2009.136(4):p.586-91.
68. Xu, B., et al., A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate,2010.70(5):p.467-72.
69. Hu, Z., et al., Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest,2008.118(7):p.2600-8.
70. Zhu, Z., et al., Genetic variation of miRNA sequence in pancreatic cancer. Acta Biochim Biophys Sin (Shanghai),2009.41(5):p.407-13.
71. Giannakakis, A., et al., miRNA genetic alterations in human cancers. Expert Opin Biol Ther,2007.7(9):p.1375-86.
72. Yang, J., et al., Analysis of sequence variations in 59 microRNAs in hepatocellular carcinomas. Mutat Res,2008.638(1-2):p.205-9.
73. Calin, G.A. and C.M. Croce, MicroRNA-cancer connection:the beginning of a new tale. Cancer Res,2006.66(15):p.7390-4.
74. Gregory, R.I. and R. Shiekhattar, MicroRNA biogenesis and cancer. Cancer Res,2005.65(9):p.3509-12.
75. Ferdin, J., T. Kunej, and G.A. Calin, Non-coding RNAs:identification of cancer-associated microRNAs by gene profiling. Technol Cancer Res Treat, 2010.9(2):p.123-38.
76. Du, L. and A. Pertsemlidis, microRNAs and lung cancer:tumors and 22-mers. Cancer Metastasis Rev,2010.29(1):p.109-22.
77. Oulas, A., M. Reczko, and P. Poirazi, MicroRNAs and cancer-the search begins! IEEE Trans Inf Technol Biomed,2009.13(1):p.67-77.
78. Yanaihara, N., et al., Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell,2006.9(3):p.189-98.
79. Calin, GA., et al., MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A,2004.101(32):p. 11755-60.
80. Lu, J., et al., MicroRNA expression profiles classify human cancers. Nature, 2005.435(7043):p.834-8.
81. Rosenfeld, N., et al., MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol,2008.26(4):p.462-9.
82. Li, W., et al., Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer,2008.123(7):p.1616-22.
83. Guo, Y., et al., Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res,2008.68(1):p.26-33.
84. Varnholt, H., et al., MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology,2008.47(4):p. 1223-32.
85. Jiang, J., et al., Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res,2008.14(2):p.419-27.
86. Budhu, A., et al., Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology,2008.47(3):p.897-907.
87. Kutay, H., et al., Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem,2006.99(3):p.671-8.
88. Gregory, R.I., et al., The Microprocessor complex mediates the genesis of microRNAs. Nature,2004.432(7014):p.235-40.
89. Tricoli, J.V. and J.W. Jacobson, MicroRNA:Potential for Cancer Detection, Diagnosis, and Prognosis. Cancer Res,2007.67(10):p.4553-5.
90. Lawrie, C.H., et al., Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol,2008.141(5):p.672-5.
91. Mitchell, P.S., et al., Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A,2008.105(30):p.10513-8.
92. Chen, X., et al., Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res,2008. 18(10):p.997-1006.
93. Ng, E.K., et al., Differential expression of microRNAs in plasma of patients with colorectal cancer:a potential marker for colorectal cancer screening. Gut,2009.58(10):p.1375-81.
94. Huang, Z., et al., Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer,2009.
95. Resnick, K.E., et al., The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol,2009.112(1):p.55-9.
96. Heneghan, H.M., et al., Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg,2010.251(3):p.499-505.
97. Wang, K., et al., Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A,2009.106(11):p. 4402-7.
98. Wang, G.K., et al., Eur Heart J,2010.31 (6):p.659-66.
99. Tijsen, A.J., et al., MiR423-5p As a Circulating Biomarker for Heart Failure. Circ Res,2010.
100. Wang, J.F., et al., Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun,2010.
101. Ai, J., et al., Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun,2010.391(1): p.73-7.
102. Cheng, Y., et al., A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond),2010.
103. Tsujiura, M., et al., Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer,2010.
104. Wang, J., et al., MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila Pa),2009.2(9):p.807-13.
105. Hu, Z., et al., Serum MicroRNA Signatures Identified in a Genome-Wide Serum MicroRNA Expression Profiling Predict Survival of Non-Small-Cell Lung Cancer. J Clin Oncol,2010.
106. Ji, X., et al., Plasma miR-208 as a biomarker of myocardial injury. Clin Chem,2009.55(11):p.1944-9.
107. Vlassov, V.V., P.P. Laktionov, and E.Y. Rykova, Circulating Nucleic Acids as a Potential Source for Cancer Biomarkers. Curr Mol Med,2010.
108. Chin, L.J. and F.J. Slack, A truth serum for cancer-microRNAs have major potential as cancer biomarkers. Cell Res,2008.18(10):p.983-4.
109. Rosell, R., J. Wei, and M. Taron, Circulating MicroRNA Signatures of Tumor-Derived Exosomes for Early Diagnosis of Non-Small-Cell Lung Cancer. Clin Lung Cancer,2009.10(1):p.8-9.
110. van Niel, G., et al., Exosomes:a common pathway for a specialized function. J Biochem,2006.140(1):p.13-21.
111. Valadi, H., et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol,2007. 9(6):p.654-9.
112. Liu, C.J., et al., Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis,2010.
113. Michael, A., et al., Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis,2010.16(1):p.34-8.
114. Park, N.J., et al., Salivary microRNA:discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res,2009.15(17):p. 5473-7.
115. Gilad, S., et al., Serum microRNAs are promising novel biomarkers. PLoS One,2008.3(9):p. e3148.
116. Chim, S.S., et al., Detection and characterization of placental microRNAs in maternal plasma. Clin Chem,2008.54(3):p.482-90.
117. Laterza, O.F., et al., Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury. Clin Chem,2009.55(11):p.1977-83.
118. Wang, GK., et al., Circulating microRNA:a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J,2010. 31(6):p.659-66.
119. Hunter, M.P., et al., Detection of microRNA expression in human peripheral blood microvesicles. PLoS One,2008.3(11):p. e3694.
120. Rabinowits, G., et al., Exosomal microRNA:a diagnostic marker for lung cancer. Clin Lung Cancer,2009.10(1):p.42-6.
121. Simpson, R.J., et al., Exosomes:proteomic insights and diagnostic potential. Expert Rev Proteomics,2009.6(3):p.267-83.
122. Taylor, D.D. and C. Gercel-Taylor, MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol,2008. 110(1):p.13-21.
123.景花,宋沁馨,周国华.MicroRNA定量检测方法的研究进展.遗传,2010.32(1)：p.31-40.
124. Liu, C.G., et al., MicroRNA expression profiling using microarrays. Nat Protoc,2008.3(4):p.563-78.
125. Liu, C.G., et al., Expression profiling of microRNA using oligo DNA arrays. Methods,2008.44(1):p.22-30.
126. Lodes, M.J., et al., Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One,2009.4(7):p. e6229.
127. Lao, K., et al., Multiplexing RT-PCR for the detection of multiple miRNA species in small samples. Biochem Biophys Res Commun,2006.343(1):p. 85-9.
128. Tang, F., et al.,220-plex microRNA expression profile of a single cell. Nat Protoc,2006.1(3):p.1154-9.
129.王芳,余佳,张俊武.小RNA(MicroRNA)研究方法.中国生物化学与分子生物学报,2006.22(10)：p.772-779.
130.滕晓坤,肖华胜.基因芯片与高通量DNA测序技术前景分析.中国科学C辑：生命科学,2008.38(10)：p.891-899.
131. Cho, W.C., MicroRNAs:Potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol,2009.
132. Cortez, M.A. and GA. Calin, MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther,2009. 9(6):p.703-711.
133. Vlassov, V.V., P.P. Laktionov, and E.Y. Rykova, Circulating nucleic acids as a potential source for cancer biomarkers. Curr Mol Med,2010.10(2):p. 142-65.
134. Chan, K.C. and Y.M. Lo, Circulating tumour-derived nucleic acids in cancer patients:potential applications as tumour markers. Br J Cancer,2007.96(5): p.681-5.
[1]Fang Y, Shang QL, Liu JY, Li D, Xu WZ, Teng X, et al. Prevalence of occult hepatitis B virus infection among hepatopathy patients and healthy people in China. J Infect 2009;58(5):383-388.
[2]Zhou H, Wang H, Zhou D, Wang Q, Zou S, Tu Q, et al. Hepatitis B virus-associated intrahepatic cholangiocarcinoma and hepatocellular carcinoma may hold common disease process for carcinogenesis.[Epub ahead of print] Eur J Cancer March 8,2010 as doi:10.1016/j.ejca.2010.02.005.
[3]Aravalli RN, Steer CJ, Cressman EK. Molecular Mechanisms of Hepatocellular Carcinoma. Hepatology 2008;48(6):2047-2063.
[4]Thorgeirsson SS, Lee J-S, Grisham JW. Functional Genomics of Hepatocellular Carcinoma. Hepatology 2006;43(2) Suppl:S145-150.
[5]Bartel DP. MicroRNAs:target recognition and regulatory functions. Cell 2009; 136(2):215-233.
[6]Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature 2005;435(7043):834-838.
[7]Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 2008; 299(4):425-436.
[8]Anglicheau D, Sharma VK, Ding R, Hummel A, Snopkowski C, Dadhania D, et al. MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci USA 2009; 106(13):5330-5335.
[9]Li S, Chen X, Zhang H, Liang X, Xiang Y, Yu C, et al. Differential Expression of MicroRNAs in Mouse Liver under Aberrant Energy Metabolic Status. J Lipid Res 2009;50(9):1756-1765.
[10]Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105(30):10513-10518.
[11]Chen Xi, Ba Yi, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008;18(10):997-1006.
[12]Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE. The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 2009;112:55-59.
[13]Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 2008; 141:672-674.
[14]Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, et al. Differential expression of microRNAs in plasma of colorectal cancer patients:A potential marker for colorectal cancer screening. Gut 2009;58:1375-1381.
[15]Ai J, Zhang R, Li Y, Pu J, Lu Y, Jiao J, et al. Circulating microRNA-1 as a potential novel biomarkers for acute myocardial infarction. Biochem Biophys Res Commun 2010;391(1):73-77.
[16]Ji X, Takahashi R, Hiura Y, Hirokawa G, Fukushima Y, Iwai N. Plasma miR-208 as a Biomarker of Myocardial Injury. Clin Chem 2009;55(11):1944-1949.
[17]Li W, Xie L, He X, Li J, Tu K, Wei L, et al. Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer 2008; 123(7): 1616-1622.
[18]Ladeiro Y, Couchy G, Balabaud C, Bioulac-Sage P, Pelletier L, Rebouissou S, et al. MicroRNA Profiling in Hepatocellular Tumors Is Associated with Clinical Features and Oncogene/Tumor Suppressor Gene Mutations. Hepatology 2008;47(6): 1955-1963.
[19]Connolly E, Melegari M, Landgraf P, Tchaikovskaya T, Tennant BC, Slagle BL, et al. Elevated Expression of the miR-17-92 Polycistron and miR-21 in Hepadnavirus-Associated Hepatocellular Carcinoma Contributes to the Malignant Phenotype. Am J Pathol 2008; 173(3):856-864.
[20]Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 2006;25(17):2537-2545.
[21]Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu Z, et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 2009; 106(11):4402-4407.
[22]Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protocols 2008;3(6):1101-1108.
[23]Livak KJ, Schmittgent TD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and 2-ΔΔCT Method. Mehtods 2001;25:402-408.
[24]Zhu W, Qin W, Atasoy U, Sauter ER. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes 2009;2:89.
[25]Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, et al. MicroRNAs in Plasma of Pancreatic Ductal Adenocarcinoma Patients as Novel Blood-Based Biomarkers of Disease. Cancer Prev Res 2009;2(9):807-813.
[26]Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, et al. Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PloS ONE 2009;4(5):e5532.
[27]Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 2010;251(3):499-505.
[28]Sakamoto M, Mori T, Masugi Y, Effendi K, Rie I, Du W. Candidate molecular markers for histological diagnosis of early hepatocellular carcinoma. Intervirology 2008;51(S1):42-45.
[29]Tang F, Hajkova P, Barton SC, O'Carroll D, Lee C, Lao K, et al.220-plex microRNA expression profile of a single cell. Nat Protocols 2006; 1(3):1154-1159.
[30]Mestdagh P, Feys T, Bernard N, Guenther S, Chen C, Speleman F, et al. High-throughput stem-loop RT-qPCR miRNA expression profiling using minute amounts of input RNA. Nucl Acids Res 2008;36(21):e143.
[31]Hu Zh, Chen X, Zhao Y, Tian T, Jin G, Shu Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol [Epub ahead of print],2010 as doi:10.1200/JCO.2009.24.9342.
[1]刘永学,高月.应激研究进展.中国病理生理杂志,2002,18(2)；218-.
[2]Clark VR, Moore CL, Adams JH. Cholesterol concentrations and cardiovascular reactivity to stress in African American college volunteers. J Behav Med,1998,21(5):505-
[3]McCann BS, Benjamin GA,Wilkinson CW, et al. Plasma lipid concentrations during episodic occupational stress. Ann Behav Med,1999,21 (2):103-.
[4]Grundy S, Griffin A.C. Effects of Periodic Mental Stress on Serum Cholesterol Levels. Circulation,1959,19;496-.
[5]Siegrist J, Peter R, Cremer P, et al. Chronic work stress is associated with atherogenic lipids and elevated fibrinogen in middle aged men. J Intern Med, 1997,242(2):149-.
[6]Bachen EA, Muldoon MF, Matthews KA, et al. Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress. Psychosom Med,2002,64(4):587-