早期食管鳞癌进展转移相关分子遗传学标志物的筛选
|
摘要
背景：食管鳞癌是我国癌症疾患的主要病种之一,早期诊断早期治疗具有重要意义。随着肿瘤诊治理念的进步,近年对早期食管鳞癌探索实施局部粘膜切除术等新方案,达到在避免过度治疗的前提下根治肿瘤的目的。新方案所面临的关键问题是能否正确选择适应症。目前无论是对活检标本病理学检查和其他影像学检查均难以判断肿瘤的进展和转移倾向。肿瘤进展转移是一个极其复杂的多基因参与,多基因调控的过程,因此从分子水平上检测与肿瘤相关遗传学的改变,寻找和揭示与早期食管鳞癌进展和转移相关的分子生物学标志物,从而提供判断或预测肿瘤进展转移的分子水平依据是本项目研究探索的主要目标。本研究采用微阵列比较基因组杂交(Array-based Comparative genomic hybridization, Array-CGH)及TaqMan Human MicroRNA芯片技术,试图从早期食管鳞癌组织的“DNA片段拷贝数变化谱型”及"microRNA表达谱”中筛选出有鉴别意义的扩增(或缺失)基因／染色体区段和microRNA,以此作为早期食管鳞癌进展转移潜能相关的标志物,从而为选择正确的治疗方案提供科学依据。
方法：第一部分：采用Array-CGH技术检测24例T1N0期食管鳞癌组织中全基因组染色体DNA拷贝数改变,研究病例中11例患者术后40月内死亡(死亡组),13例患者术后生存80月以上(生存组)。第二部分：采用TaqMan Human MicroRNA Arrays技术分析第一部分所用两组病例中的16例microRNA表达情况：生存组和死亡组各选取前8例。通过以上技术分析早期食管鳞癌组织全基因组染色体拷贝数改变及microRNA表达与肿瘤进展及转移等预后关系。
结果：1、两组样品中共有多条染色体发生变化,其中最常见的染色体基因组扩增发生在1 q、3 q、5p、6p、7q／p、8q／p、9q、11 q、12p、14q、16p、17 q／p、18p、19 q／p、20 q／p和22q染色体区段上,在染色体3p、4q／p、5q、6p、9p、11 q、13 q、14q、18q、19q、21q中常见染色体基因组缺失。与死亡组相比较,生存组更易出现包括染色体1 q、3q、5p、7q／p、8q／p、9q、11 q、12p、14q、16p、17q、19q、20q和22q扩增和染色体4q／p、5q和13q缺失。两组差异性小片段DNA拷贝数改变主要为1q21.3-23.3、3q21.1-24、3q26.1-26.33、5p13.1-15.31、7p22、7q11.23、8p11.2、8q22.1-24.3、11q12.1-13.5、12p12.1-13.33、14q23.1、16p12.1-13.3、17q25.1、19q13.12、20q11.21-13.33、22q12.1-13.2扩增及4p、4q31-35、5q22.3、13q12.21-12.2缺失。进一步分析发现,109个基因及探针可将死亡组与生存组区分开来(p<0.01)。2、两组样品中多个microRNA表达发生改变,经过组间对比,其中四个microRNA表达具有统计学意义(p<0.05),包括：miR-574-3p、MiR-19b、miR-31及miR-28-3p。
结论：在早期食管鳞癌显著不同生存期患者的染色体DNA拷贝数变化及microRNA表达变化中,存在特定的染色体区段或基因及microRNA,可能决定肿瘤进展转移潜能。所筛选出的基因组DNA拷贝数改变及相关基因和microRNA有可能成为早期食管鳞癌预测进展转移和预后的分子标志物,从而为早期食管鳞癌患者选择正确的治疗方案提供科学依据。
Background:Esophageal squamous cell carcinoma (ESCC), especially in northern China, is one of the common fatal cancers. ESCC is an aggressive cancer with poor prognosis. Most patients present with advanced stage disease when they were diagnosed, so they lost the best time for therapy. Early detection and therapay remains the best way for a cure. With the improvement of tumor therapy, the recommended therapy of early ESCC is endoscopic mucosal resection (EMR). The key point for EMR is to estimate the condition of infiltration of lesions and metastasis exactly, and the metastasis condition of lymph node directly determines the treatment modes. However, there are no effective examinations to evaluate the progression and metastasis of tumors. The most important reason for different tumors with different biological behaviours is that each tumor has its characteristic genetic alterations. Unfortunately there are no specific makers of the genetic alterations for progression and metastasis of tumors, so it would significantly be rational strategies to systemically analyze cancer tissues on molecular level and to find specific molecular markers for progression and metastasis. The aim of this study is to screen out ideal markers for predicting progression and metastasis of early ESCC.
Methods:The first part:surgically resected specimens from 24 patients with early ESCC(T1N0 stage), were studied. According to the survival time, they were divided into two groups. Patients in death group were 11 cases who died in 40 months and patients in survival group were 13 cases with at least 80 months duration. The genomic DNA isolated from tumor tissues were hybridized to Agilent CGH microarray. The second part:16 of 24 were analyzed for expression of microRNAs by TaqMan Human MicroRNA Arrays.16 cases were divided into two groups based on the same standard.
Results:1. Many chromosome alterations were identified in our study, including gains of 1q,3q,5p,6p,7q/p,8q/p,9q, 11q,12p,14q,16p,17q/p,18p, 19q/p,20q/p,22q and deletions of 3p,4q/p,5q,6p,9p,11q,13q,14q,18q,19q,21q. Compared with death group, some copy number changes occurred more frequent in survival group. They were gains of 1q,3q,5p,7q/p,8q/p,9q, 11q,12p,14q,16p, 17q,19q,20q,22q and loss of 4q/p,5q,13q. Some small scale changes occurred in the two groups were significantly different. They included gains of lq21.3-24, 3q21.1-24,3q26.1-26.33,5p13.1-15.31,7p22,7q11.23,8p11.2,8q22.1-24.3, 11q12.1-13.5,12p12.1-13.33,14q23.1,16p12.1-13.3,17q25.1,19q13.12, 20q11.21-13.33,22q12.1-13.2 and losses of 4p,4q31-35,5q22.3 and 13q12.21-12.2. Moreover,109 candidate genes for distinguishing the two groups were identified.2. Many microRNAs were found to be differently expressed between two groups in our study, and four microRNAs were identified for distinguishing these two groups. They include miR-574-3p, miR-19b, miR-31 and miR-28-3p.
Conclusions:There are some specific changes of chromosome copy number, genes and microRNAs which might contribute to the potency for progression and metastasis of early ESCC.In our study, we screened out some specific markers of molecular genetics to predict the progression and metastasis of early ESCC. These markers included 109 genes with copy number changes and four microRNAs. The results of our study find the scientific proof for correct estimation on therapy of early ESCC.
方法：第一部分：采用Array-CGH技术检测24例T1N0期食管鳞癌组织中全基因组染色体DNA拷贝数改变,研究病例中11例患者术后40月内死亡(死亡组),13例患者术后生存80月以上(生存组)。第二部分：采用TaqMan Human MicroRNA Arrays技术分析第一部分所用两组病例中的16例microRNA表达情况：生存组和死亡组各选取前8例。通过以上技术分析早期食管鳞癌组织全基因组染色体拷贝数改变及microRNA表达与肿瘤进展及转移等预后关系。
结果：1、两组样品中共有多条染色体发生变化,其中最常见的染色体基因组扩增发生在1 q、3 q、5p、6p、7q／p、8q／p、9q、11 q、12p、14q、16p、17 q／p、18p、19 q／p、20 q／p和22q染色体区段上,在染色体3p、4q／p、5q、6p、9p、11 q、13 q、14q、18q、19q、21q中常见染色体基因组缺失。与死亡组相比较,生存组更易出现包括染色体1 q、3q、5p、7q／p、8q／p、9q、11 q、12p、14q、16p、17q、19q、20q和22q扩增和染色体4q／p、5q和13q缺失。两组差异性小片段DNA拷贝数改变主要为1q21.3-23.3、3q21.1-24、3q26.1-26.33、5p13.1-15.31、7p22、7q11.23、8p11.2、8q22.1-24.3、11q12.1-13.5、12p12.1-13.33、14q23.1、16p12.1-13.3、17q25.1、19q13.12、20q11.21-13.33、22q12.1-13.2扩增及4p、4q31-35、5q22.3、13q12.21-12.2缺失。进一步分析发现,109个基因及探针可将死亡组与生存组区分开来(p<0.01)。2、两组样品中多个microRNA表达发生改变,经过组间对比,其中四个microRNA表达具有统计学意义(p<0.05),包括：miR-574-3p、MiR-19b、miR-31及miR-28-3p。
结论：在早期食管鳞癌显著不同生存期患者的染色体DNA拷贝数变化及microRNA表达变化中,存在特定的染色体区段或基因及microRNA,可能决定肿瘤进展转移潜能。所筛选出的基因组DNA拷贝数改变及相关基因和microRNA有可能成为早期食管鳞癌预测进展转移和预后的分子标志物,从而为早期食管鳞癌患者选择正确的治疗方案提供科学依据。
Background:Esophageal squamous cell carcinoma (ESCC), especially in northern China, is one of the common fatal cancers. ESCC is an aggressive cancer with poor prognosis. Most patients present with advanced stage disease when they were diagnosed, so they lost the best time for therapy. Early detection and therapay remains the best way for a cure. With the improvement of tumor therapy, the recommended therapy of early ESCC is endoscopic mucosal resection (EMR). The key point for EMR is to estimate the condition of infiltration of lesions and metastasis exactly, and the metastasis condition of lymph node directly determines the treatment modes. However, there are no effective examinations to evaluate the progression and metastasis of tumors. The most important reason for different tumors with different biological behaviours is that each tumor has its characteristic genetic alterations. Unfortunately there are no specific makers of the genetic alterations for progression and metastasis of tumors, so it would significantly be rational strategies to systemically analyze cancer tissues on molecular level and to find specific molecular markers for progression and metastasis. The aim of this study is to screen out ideal markers for predicting progression and metastasis of early ESCC.
Methods:The first part:surgically resected specimens from 24 patients with early ESCC(T1N0 stage), were studied. According to the survival time, they were divided into two groups. Patients in death group were 11 cases who died in 40 months and patients in survival group were 13 cases with at least 80 months duration. The genomic DNA isolated from tumor tissues were hybridized to Agilent CGH microarray. The second part:16 of 24 were analyzed for expression of microRNAs by TaqMan Human MicroRNA Arrays.16 cases were divided into two groups based on the same standard.
Results:1. Many chromosome alterations were identified in our study, including gains of 1q,3q,5p,6p,7q/p,8q/p,9q, 11q,12p,14q,16p,17q/p,18p, 19q/p,20q/p,22q and deletions of 3p,4q/p,5q,6p,9p,11q,13q,14q,18q,19q,21q. Compared with death group, some copy number changes occurred more frequent in survival group. They were gains of 1q,3q,5p,7q/p,8q/p,9q, 11q,12p,14q,16p, 17q,19q,20q,22q and loss of 4q/p,5q,13q. Some small scale changes occurred in the two groups were significantly different. They included gains of lq21.3-24, 3q21.1-24,3q26.1-26.33,5p13.1-15.31,7p22,7q11.23,8p11.2,8q22.1-24.3, 11q12.1-13.5,12p12.1-13.33,14q23.1,16p12.1-13.3,17q25.1,19q13.12, 20q11.21-13.33,22q12.1-13.2 and losses of 4p,4q31-35,5q22.3 and 13q12.21-12.2. Moreover,109 candidate genes for distinguishing the two groups were identified.2. Many microRNAs were found to be differently expressed between two groups in our study, and four microRNAs were identified for distinguishing these two groups. They include miR-574-3p, miR-19b, miR-31 and miR-28-3p.
Conclusions:There are some specific changes of chromosome copy number, genes and microRNAs which might contribute to the potency for progression and metastasis of early ESCC.In our study, we screened out some specific markers of molecular genetics to predict the progression and metastasis of early ESCC. These markers included 109 genes with copy number changes and four microRNAs. The results of our study find the scientific proof for correct estimation on therapy of early ESCC.
引文
1.2009中国卫生统计年鉴：2004年-2005年中国恶性肿瘤死亡抽样回顾调查。
2. Wang GQ, Jiao GG, Chang FB, et al. Long-term results of operation for 420 patients with early squamous cell esophageal carcinoma discovered by screening. Ann Thorac Surg.2004,77(5):1740-1744.
3. Ponec RJ, Kimmey MB. Endoscopic therapy of esophageal cancer. Surg Clin North Am.1997,77:1197-1217.
4. Nakajima Y. Nagai K, Miyake S, et al. Evaluation of an indicator for lynphnode metastasis of esophageal squamous cell carcinoma invading the submucosal layer. Jpn. J Cancer Res.2002,93:305-312.
5. Yanai H. Harada T, Okamoto T, et al. Prognostic value and interobserver agreement of endoscopic ultrasongraphy for superficial squmous cell carcinoma of the esophagus:a prospective study. Int J Gastrointest Cancer.2003,34(1):1-8.
6. Araki K, Ohno S, Egashira A. et al. Pathologic features of superficial esophageal squmous cell carcinoma with lymph node and distal metastasis. Cancer.2002, 94(2):570-575.
7. Herbst RS, Lippman SM. Molecular signatures of lung cancer-to ward personalized therapy. N Eng J Med.2007,356(1):76-78.
8. Kallioniemi A, Kallioniemi OP, Sudar D, etal. Comparative genomic hibridization for molecular cytogenetic analysis of solid tumors.Science,1992,258:818-821.
9. Lerman MI, Minna JD, et al. Tumor suppressor genes on chromosone3p involved in the patho-genesis of lung and other cancers. oncogene,2002,21(45):6915-6935.
10. Wu MS, Chang MC,Huang SP, et al. Correlation of histologic subtypes and replication error phenotype with Comparative genomich ybridization in gastric cancer.Genes Chromosones Cancer,2001,30(1):80-86.
11. DeAngelis PM, Stokke T, Beigi M, etal.Prognostic significance of recurrent chromosome alaberrations detected By comparative genomic hybridization in sporadic colorectal cancer. Int J Colorectal Dis,2001,16(1):38-45.
12. Pestova E, Wilber K, King W. Microarray based CGH in cancer.Methods Mol Med, 2004,97:355-375.
13. Su M, Chin SF, Li XY, et al. Comparative genomic hybridization of esophageal adenocarcinoma and squamous cell carcinoma cell lines. Dis Esophagus.2006, 19:10-14.
14. Sugimoto T, Arai M, Shimada H, et al. Integrated analysis of expression and genome alteration reveals putative amplified target genes in esophageal cancer. Oncol Rep.2007,18:465-472.
15. Kuwano H, Kato H, Miyazaki T, et al. Genetic alterations in esophageal cancer. Surg Today.2005,35:7-18.
16. Wu YP, Yang YL, Yang GZ, et al. Identification of chromosome aberrations in esophageal cancer cell line KYSE180 by multicolor fluorescence in situ hybridization. Cancer Genet Cytogenet.2006,170:102-107.
17. Marilanda FB, Ana ES, Marileila VG Genomic imbalances in esophageal squamous cell-carcinoma identified by molecular cytogenetic techniques. Genet-Mol. Biol., ahead of print Epub Apr 02,2010.
18.张旭,朱志华,林鹏等。食管不典型增生和早期食管鳞癌全基因组的变化特征分析。中华医学杂志,2008 Oct 14；88(37)：2636-2641.
19. Qin YR, Wang LD, Dora K, et al.Genomic changes in primary lesion and lymph node metastases of esophageal squamous cell carcinoma. Ai Zheng,2005, 24:1048-1053.
20. Qin YR, Wang LD, Kwong D, et al. Comparative genomic hybridization:The profile of chromosomal imbalances in esophageal squamous cell carcinoma. Zhonghua Bing Li Xue Za Zhi.2005,34:80-83.
21. Qin YR, Wang LD, Fan ZM, et al. Comparative genomic hybridization analysis of genetic aberrations associated with development of esophageal squamous cell carcinoma in Henan, China. World J Gastroenterol.2008,14:1828-1835.
22. Carneiro A, Isinger A, Karlsson A, et al.Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer. BMC Cancer,2008,8:98-107.
23. Wang LD, Qin YR, Fan ZM, et al. Comparative genomic hybridization:Comparison between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-incidence area for both cancers in Henan, northern China. Dis Esophagus.2006,19:459-467.
24. Yen CC, Chen YJ, Chen JT, et al. Comparative genomic hybridization of esophageal squamous cell carcinoma:correlations between chromosomal aberrations and disease progression/prognosis. Cancer,2001,92(10):2769-2777.
25. Ueno T, Tangoku A, Yoshino S, et al. Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma. Clin Cancer Res,2003 Nov 1,9 (14):5137-5141.
26. Ueno T, Tangoku A, Yoshino S, et al. Gain of 5p15 detected by comparative genomic hybridization as an independent marker of poor prognosis in patients with esophageal squamous cell carcinoma. Clin Cancer Res,2002,8:526-533.
27. Fujita Y, Sakakura C, Shimomura K, et al. Chromosome arm 20q gains and other genomic alterations in esophageal squamous cell carcinoma, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization. Hepatogastroenterology.2003,50:1857-1863.
28. Xu FP, Xie D, Wen JM, et al. SRC-3/AIB1 protein and gene amplification levels in human esophageal squamous cell carcinomas. Cancer Lett.2007,245:69-74.
29. Shay JW, Wright WE. Implications of mapping the human telomerase gene (hTERT) as the most distal gene on chromosome 5p.Neoplasia,2000,2:195-201.
30. Bieche I, Nogues C, Paradis V et al. Quantitation of hTERT gene expression in sporadic breast tumors with a real-time reverse transcription-polymerase chain reaction assay. Clin Cancer Res,2000:452-459.
31. Komiya T, Kawase I, Nitia T ei al. Prognostic significance of hTERT expression in non-small cell lung cancer. Int. J. Oncol,2000,16:1173-1177.
32. Akervall JA. Michalides RJ. Mineta H, et al. Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclinD1 overexpression. Cancer,1997,79:380-389.
33. Mandard AM, Hainaut P, Hollstein M. Genetic steps in the development of squamous cell carcinoma of the esophagus. Mutat Res,2000,462:335-342.
34. Bockmuhl U, Schluns K, Kuchler I, et al. Genetic imbalances with impact on survival in head and neck cancer patients. Am. J. Pathol,2000,157:369-375.
35. Rodrigo JP, Garcia LA, Ramos S, et al. EMS1 gene amplification correlates with poor prognosis in squamous cell carcinomas of the head and neck. Clin Cancer Res, 2000,6:3177-3182.
36. Sunpaweravong P, Sunpaweravong S, Puttawibul P, et al. Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res.2005,131:111-119.
37. Naohide K, Masato H, Kuniko O, et al. Expression of TMEFF1 mRNA in the mouse central nervous system precise exam ination and comparative studies of TMEFF1 and TMEFF2. Mol Bra Res,2001,86:48—55.
38. Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet,1999,21: 163-167.
39. Matthias PA, Ebert W, Suzanne H. et al. Hypermethylation of the TPEF/HPP1 gene in primary and metastatic colorectal canaers.Neoplasia,2005,7:771—778.
40. Field JK, Liloglou T, Warrak S, et al.Methylation discriminators in NSCLC idntified by a microarray based approach.Int J Oncol.2005,27(1):105-111.
41. Kim BH, Cho NY, Shin SH, et al.CpG island hypermethylation and repetitive DNA hypomethylation in pre malignant lesion of extrahepatic cholangiocarcinoma. Virchows Arch.2009,455(4):343-351.
42. Smith E, De Young NJ, Pavey SJ,et al. Similarity of aberrant DNA methylation in Barre's esophagus and esophageal adenocarcinoma. Mol Cancer.2008, (7) 75.
43. Tsunoda S, Smith E, De Young NJ, et al. Methylation of CLDN6, FBN2, RBP1,RBP4, TFP12, and TMEFF2 in esophageal squamous cell carcinoma. Oncol Rep.2009,21(4):1067-1073.
44. Nooij-wan Dalen AG, Van Dongen GA, Smeets SJ, et al. Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K included, as molecular markers for head-and-neck squamous cell carcinoma. Int J Cancer,2003,103 (6):768-774.
45. Choi SH, Kong HK, Park SY, et al. Metastatic effect of LY-6K gene in breast cancer cells. Int J Oncol.2009,35(3):601-607.
46. Ishikawa N, Takano A, Yasui W, et al. Cancer-Testis Antigen Lymphocyte Antigen 6 Complex Locus K Is a Serologic Biomarker and a Therapeutic Target for Lung and Esophageal Carcinomas.Cancer Res.2007,67(24):11601-11611.
47. Ferdinandusse S,Denis S,Llst L,et al.Subcellular localization and physiological role of a-methylacyl-CoA racemase.J Lipid Res,2000,4(1):1890-1896.
48. Cuebas DA,Phillips C,Schmitz W,et al.The role of a-methlyaclyl-CoA racemase in bile acid synthesis J Biochem,2002,36(3):801-807.
49. Zhou M, Chinnaiyan AM, Kleer CG, et al.Alpha-methylacyl-CoA racemase:a novel tumor marker over-expressed in several human cancers and their precursor lesions.Surg Patho,2002,26:926-931.
50. Liu W, Caqle PT, Botero RC, et al.Significance of overexpression of alpha methylacyl-coenzyme A racemase in hepatocellular carcinoma. J Exp Clin Cancer Res.2008,15; 27:2.
51. Witkiewicz AK, Varambally S, Shen R,et al. Alpha-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis. Cancer Epidemiol Biomarkes Prev.2005, 14(6):1418-1423.
52. Jiang Z, Wu CL, Woda, BA, et al. Alpha-methylacyl-CoA racemase:a multi-institutional study of a new prostate cancer marker. Histopathology.2004, 45(3):218-225.
53. Shi XY, Bhaqwandeen B, Leong AS. P16, cyclin D1, and AMACR as markers for
desplasia in Barrett esophagus. Appl Immunohistchem Mol Morphol.2008, 16(5):447-452.
54. Scheil BS, Lorenz D, Ell C, et al. expression of alpha-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett's esophagus. Mod Pathol.2008,21(8):961-967.
55. Ullrich A, Schlessinger J.Signal transduction by receptors with tyrosine kinase activity. Cell,1990,61(2):203-212.
56:Yue Y, Widmer DA, Halladay AK, et al. Specification of distinct dopaminergic neural pathways:roles of the Eph family receptor EphB1 and ligand ephrin-B2. J Neurosci.1999,19(6):2090-101.
57. Huynh DU, Vindis C, Liu H, et al.Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis. J Cell Sci.2002, 115(15):3073-81.
58. Sheng Z. Wang J, Dong Y. et al. EphBl is underexpressed in poorly differentiated colorectal cancers. Pathobiology.2008,75(5):274-280.
59. Wang JD, Dong YC, Sheng Z, et al. Loss of expression of EphBl protein in gastric carcinoma associated with invasion and metastasis.Oncology.2007,73(3-4):238-245.
60. Hu N, Wang CY, Hu Y, et al. Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array. Cancer Res.2005,65(7):2542-2546.
61. Chan KY, Lai PB, Squire JA, et al. Positionnal expression proiling indicates genes in deletion hotspots of hepatocellular carcinoma. Mod Pathol.2006,19(12):1546-1554.
62. Zhu WL, Fan BL, Liu DL, et al. Abnomal expression of fibrinogen gamma (FGG) and palsma level of fibrinogen in patients with hepatocellular carcinoma. J Thromb Haemost.2008,6(1):176-1783.
63. Sahni A, Simpson-Haidaris PJ, Sahni SK, et al. Fibrinogen synthesized by cancer cells auhments the proliferative effect of fibroblast growth factor-2 (FGF-2). J Thromb Haemost.2008,6(1):174-175.
1. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.Cell.1993,75(5):843-854.
2. Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature.2000,403(6772):901-906.
3. Brennecke J, Hipfner DR, Stark A, et al. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell.2003,113(1):25-36.
4. Xu P, Vernooy SY, Guo M, et al. The Drosophila microRNA mir-14 suppresses cell death and is required for normal fatmetabolism. CurrBiol.2003,13(9):790-795.
5. Dostie J, Mourelatos Z,Yang M, et al. Numerous microRNPs in neuronal cells containing novel microRNPs. RNA.2003,9(2):180-186.
6. Chen CZ, Li L, Lodish HF, et al. MicroRNAs modulate hemato-poietic lineage differentiation. Science.2004,303(5654):83-86.
7. Calin GA, Sevignani C, Dumitru CD,et al.Human mcroRNA genes are frequently located at fragile sites and genomic regions involved in cancers.Proc Natl Acad Sci USA.2004,101(9):2999-3004.
8. He L, Thomson JM, Hemannm T, etal.A microRNA poly-cistron as a potential human oncogene. Nature.2005,435:828-833.
9. O'Donnell KA, Wentzel EA, Zeller KI, et al.c-Myc-regulated microRNAs modulate E2F1 expression. Nature.2005,435(7043):839-843.
10. Monik AW, Kerstin B, et al. High expression of precursor microRNA-15/BICRNA in children with Burkitt lym-phoma.Genes, Chromosomes&Cancer.2004,39:167-169.
11. Eisp S, Tam W, Sun L, et al. A ccumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA.2005,102(10):3627-3632.
12. Voorhoeve PM, Agami R. The tumor-suppressive functions of the human INK4A locus. Cancer Cell.2003,4(4):311-319.
13. Takamizawa J, KonishiH, YanagisawaK, etal. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res.2004,64(11):3753-3756.
14. Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family.Cell 2005.120(5):635-647.
15. Cimmino A, Calin GA, Fabbri M, et al miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA.2005,102(39):13944-13949.
16. Karube Y, Tanaka H, Osaka H, et al. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci.2005,96(2):111-115.
17. Omoto S, Fujii YR. Regulation ofhuman immunodeficiency virusl transcription by nefmicroRNA. J GenViro.2005,86(Pt3):751-755.
18. Peeffer S, Zavolan M, Grosser FA, et al. Identification Of virus-encoded microRNAs. Science.2004,304:734-736.
19. Lu J, Getz G, Miska EA,et al. MicroRNA expression profiles classify human cancers. Nature.2005,435 (7043):834-838.
20. Calin GA, Ferracin M, Cmi Mino A, et al. A microRNA signature associatedwith prognosis and progression in chron-ic lymphocytic leukemia. N Eng J Med.2005, 353(17):1793-1801.
21. lorio MV, Ferracin M, Liu CG,et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res.2005,65(16):7065-7070.
22. Feber A, Xi L, Luketich JD, et al.MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg.2008,135(2):255-260.
23. Guo Y, Chen Z, Zhang L, et al. Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res.2008; 68(1):26-33.
24. Lee KH, Goan YG, Hsiao M, et al.microRNA-373(miR-373)post-transcriptionally regulates large tumor suppressor, homolog2(LATS2) and stimulates proliferation in human esophageal cancer.Exp Cell Res.2009,315(15):2529-2538.
25. Hiyoshi Y. Kamohara H. Karashima R. et al.. MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clin Cancer Res. 2009,15(6):1915-1922.
26. Hu Y, Correa AM, Hoque A, et al. prognostic significance of differentially expressed miRNAs in esophageal cancer. Int J Cancer.2010 Mar 22.[Epub ahead of print] 30e 16-22.
27. Oqawa R, Ishiquro H, Kuwabara Y, et al. expression profiling of micro-RNAs in human esophageal squmous cell carcinoma using RT-PCR. Med Mol Morphol.2009, 42(2):102-109.
28. He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature.2005,435(7043):828-833.
29. Ventura A, Young AG, Winslow MM, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008,132(5):875-886.
30. Koralov SB, Muljo SA, Galler GR, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell.2008,132(5):860-874.
31. Lu Y, Thomson JM, Wong HY, et al. Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol.2007,310(2):442-453.
32. Lu Y, Okubo T, Rawlins E, et al. Epithelial progenitor cells of the embryonic lung and the role of microRNAs in their proliferation. Proc Am Thorac Soc.2008,5(3): 300-304.
33. Suarez Y, Fernandez-hernando C, Yu J, et al. Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci USA.2008, 105(37):14082-14087.
34. Wang Q, Li YC, Wang J, et al. miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci USA.2008,105(8):2889-2894.
35. O'Donnel KA, Wentzel EA, Zeller KI, et al. C-myc-regulated microRNAs modulate E2F1 expression. Proc Natl Acad Sci USA.2005,435(7043):839-843.
36. Rinaldi A, Poretti G, Kwee I, et al. Concomitant MYC and microRNA cluster miR-17-92 (C13orf25) amplification in human mantle cell lymphoma. Leuk Lymphoma.2007,48(2):410-412.
37. Kutay H, Bai S, Datta J, et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem.2006,99(3):671-678.
38. Gottardo F, Liu CG, Ferracin M, et al.Micro-RNA profiling in kidney and bladder cancers. Urol Oncol.2007,25(5):387-392.
39. Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA.2006,103(7): 2257-2261.
40. Ota A, Tagawa H, Karnan S, et al.Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res.2004,64(9):3087-3095.
41. Anzick SL, Kononen J, Walker RL, et al. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science.1997,277(5328):965-968.
42. Wang Y, Wu MC, Sham JS, et al.Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer.2002,95(11):2346-2352.
43. Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol.2006,26(21): 8191-8201.
44. Valastyan S, Reinhardt F, Benaich N et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell.2009,137,1032-1046.
45. Valastyan S, Benajch N, Chang A. et al. Concomitant suppression of three target genes can explain the impact of microRNA on metastasis. Genes Dev.2009, Nov 15; 23 (22):2592-7.
46. Bandres E, Cubedo E, Aqirre X, et al. Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. MOL Cancer.2006, Jul 19; 5:29.
47. Liu X, Sempere LF, Ouyang H, et al. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors, J Clin Invest.2010 Apr;120(40):1298-309.
1. Pasquinelli AE, Hunter S, Bracht J,et al. MicroRNAs:a developing story.Curr Opin Genet Dev.2005,15:200-205.
2. Harfe BD. MicroRNAs in vertebrate development. Curr Opin Genet Dev.2005, 15:410-415.
3. Carleton M, Cleary MA, Linsley PS,et al. MicroRNAs and cell cycle regulation. Cell Cycle.2007,6:2127-2132.
4. Garzon R, et al. MicroRNA expression and function in cancer. Trends Mol Med. 2006,12:580-587.
5. Wang E. MicroRNA, the putative molecular control for mid-life decline. Ageing Res Rev.2007,6:1-11.
6. Boehm M, Slack FJ. MicroRNA control of lifespan and metabolism.Cell Cycle. 2006,5:837-840.
7. Calin GA, Dumitru CD, Shimizu M et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA.2002,99:15524-15529.
8. Lee RC, Feinbaum RL, Ambros V, et al. The C.elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell.1993, 75:843-854.
9. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function.Cell. 2004,116:281-297.
10. Berezikov E, Guryev V, van de Belt J, et al. Phylogenetic shadowing and computational identification of human microRNA genes. Cell.2005,120:21-24.
11. Bentwich I, Avniel A, Karov Y, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet.2005,37:766-770.
12. Cho WC. OncomiRs:the discovery and progress of microRNAs in cancers. Molecular Cancer.2007,6:60-66.
13. Cowland JB, Hother C, Gronbaek K, et al. MicroRNAs and cancer. APMIS. Journal Compilation C.2007,115:1090-1106.
14. Lee Y, et al. MicroRNA genes are transcribed by RNA polymerase Ⅱ. EMBO J. 2004; 23:4051-4060.
15. Lin, S.L., Chang D., Ying S.Y. Asymmetry of intronic pre-miRNA structures in functional RISC assembly. Gene.2005,356,32-38.
16. Gregory RI, Chendrimada TP, Shiekhattar R. MicroRNA biogenesis:isolation and characterization of the microprocessor complex. Methods Mol Biol.2006,342:33-47.
17. Bohnsack, M.T., Czaplinski K., Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediatesn nuclear export of pre-miRNAs. RNA.2004, 10,185-191.
18. Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3? UTR evolution.Cell 2005,123:1133-1146.
19. Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs downregulate large numbers of targetmRNAs. Nature 2005, 433:769-73.
20. Pattanayak, D., Agarwal S., Sumathi, S., et al. Small but mighty RNA-mediated interference in plants. Indian J. Exp. Biol.2005,43,7-24.
21. Hutvagner, G. Small RNA asymmetry in RNAi:Function in RISC assembly and gene regulation. FEBS Lett.2005,579,5850-5857.
22. Carthew, R.W. Gene regulation by microRNAs. Curr. Opin.Genet. Dev.2006,16, 203-208.
23. Castoldi M, Schmidt S, Benes V, et al. A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA.2006,12:913-920.
24. Thomson JM, Parker J, Perou CM, et al. A custom microarray platform for analysis of micro RNA gene expression. Nat Methods.2004,1:47-53.
25. Kloosterman WP, Wienholds E, de Bruijn E, et al. In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes. Nat Methods.2005. 3:27-29.
26. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature.2005,435:834-838.
27. Jiang J, Lee EJ, Gusev Y, Schmittgen TD. Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res.2005, 33:5394-5403.
28. Aoife JL, Miller N, Roisin EM, et al. MicroRNAs as Prognostic Indicators and Therapeutic Targets:Potential Effect on Breast Cancer Management. Clin Cancer Res.2008,14:360-364.
29. Dalmay T. MicroRNAs and cancer. Journal of Internal Medicine.2008,263; 366-375.
30. Fabbri M, Croce CM, Calin GA. MicroRNAs. The Cancer Journal.2008, 14(1):1-6.
31. Feber A, Xi LQ, Luketich JD, et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg.2008,135:255-260.
32. Sassen S, Miska EA, Caldas C. MicroRNA-implications for cancer, Virchows Arch.2008,452:1-10.
33. Visone R, Petrocca F, Croce CM. Micro-RNAs in Gastrointestinal and Liver Disease. Gastroenterology.2008,135:1866-1876.
34. Kumar MS, Lu J, Mercer KL, et al. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet.2007,39:673-677.
35. Calin GA, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell.2007,12:215-229.
36. Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med.2005, 353:1793-1801.
37. Cimmino A, Calin GA, Fabbri M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA.2005,102:13944-13949.
38. Garzon R, Pichiorri F, Palumbo T, et al. MicroRNAgene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia. Oncogene. 2007,26:4148-4157.
39. Bottoni A, Piccin D, Tagliati F, et al. miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol.2005,204:280-285.
40. Bandres E, Cubedo E, Agirre X, ct al. Identification by realtime PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer.2006,5:29.
41. Akao Y, Nakagawa Y, Kitade Y, et al. Downregulation of microRNAs-143 and-145 in B-cell malignancies. Cancer Sci.2007,98:1914-1920.
42. Akao Y, Nakagawa Y, Naoe T. MicroRNA-143 and-145 in colon cancer. DNA Cell Biol.2007,26:311-320.
43. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep 2006,16:845-850.
44. Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene.2007, 26:5017-5022.
45. Chang TC, Wentzel EA, Kent OA, et al.Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell.2007, 26:745-752.
46. He L, He X, Lim LP, et al.A microRNA component of the p53 tumour suppressor network. Nature.2007,447:1130-1134.
47. Yanaihara N, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell.2006,9:189-198.
48. Johnson SM, et al. RAS is regulated by the let-7 microRNA family. Cell.2005, 120:635-647.
49. Akao Y, Nakagawa Y, Naoe T. let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull.2006,29:903-906.
50. Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science.2007,315:1576-1579.
51. Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev.2007,21:1025-1030.
52. Tam W, et al. Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis. J Virol.2002, 76:4275-4286.
53. Volinia S, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA.2006,103:2257-2261.
54. Eis PS, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA.2005,102:3627-3632.
55. Costinean S, Zanesi N, Pekarsky Y, et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E (mu)-miR155 transgenic mice. Proc Natl Acad Sci USA.2006,103:7024-7029.
56. Fulci V, Chiaretti S, Goldoni M, et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood.2007,109:4944-4951.
57. Roldo C, Missiaglia E, Hagan JP, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol.2006,24:4677-4684.
58. Gironella M, et al. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA.2007,104:16170-16175.
59. Iorio MV, Ferracin M, Liu CG et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005; 65:7065-7070.
60. Si ML, Zhu S, Wu H, et al. miR-21-mediated tumor growth. Oncogene,2007, 26:2799-2803.
61. Zhu S, Si ML, Wu H, Mo YY:MicroRNA-21 Targets the tumor suppressor gene Tropomyosin 1 (TPM1). J Biol Chem.2007,282:14328-14336.
62. Wu W, et al. MicroRNA and cancer:current status and prospective. Int J Cancer. 2007,120:953-960.
63. Hayashita Y, Osada H, Tatematsu Y et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65:9628-9632.
64. Matsubara H, Takeuchi T, Nishikawa E, et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene,2007,26:6099-6105
65. He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature,2005,435:828-833.
66. Venturini L, et al. Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34_ cells. Blood.2007,109:4399-4405.
67. O'Donnell KA, et al. c-Myc-regulated microRNAs modulate E2F1 expression. Nature.2005,435:839-843.
68. Felli N, et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA.2005,102:18081-18086.
69. Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, Chiappetta G, Liu CG, Santoro M, Negrini M, Croce CM, Fusco A:MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer.2006, 13:497-508.
70. Ciafre SA, Galardi S, Mangiola A et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun.2005,334: 1351-1358.
71. Pavlidisa N, Fizazib K. Cancer of unknown primary (CUP). Crit Rev Oncol Hematol.2005,54:243-250.
72. Bloomston M, Frankel WL, Petrocca F, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA.2007,297:1901-1908.
73. Lee EJ, Gusev Y, Jiang J, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer.2007,120:1046-1054.
74. Ma L, Weinberg RA.Micromanagers of malignancy:role of microRNAs in regulating metastasis. Trends in Genetics.2008,24 (9):448-456.
75. Dews M, Homayouni A, Yu D et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet.2006,38:1060-1065.
76. Ma L, Teruya-Feldstein J, Weinberg RA.Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature.2007,449:682-688.
77. Mourad, P.D. et al. Why are systemic glioblastoma metastases rare? Systemic and cerebral growth of mouse glioblastoma. Surg.Neurol.2005.63:511-519.
78. Tavazoie, S.F. et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature.2008,451,147-152.
79. Budhu, A. et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology.2008,47:897-907.
80. Huang, Q. et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat. Cell Biol.2008,10:202-210.
81. Guo Y, Chen ZL,Zhang L. Distinctive MicroRNA Profiles Relating to Patient Survival in Esophageal Squamous Cell Carcinoma Cancer Res.2008,68:(1):26-33.
82. Visone R, Petrocca F, Croce CM. Micro-RNAs in Gastrointestinal and Liver Disease. Gastroenterology.2008,135:1866-1876.
83. Selaru FM, Zou T, Xu Y, et al. Global gene expression profiling in Barrett's esophagus and esophageal cancer:a comparative analysis using cDNA microarrays. Oncogene.2002,21:475-478.
84. Helm J, Enkemann SA, Coppola D, Barthel JS, Kelley ST, Yeatman TJ. Dedifferentiation precedes invasion in the progression from Barrett's metaplasia. Cancer Res.2008,68:(1):26-33.
85. Sugito N, Ishiguro H, Kuwabara Y et al. RNASEN Regulates Cell Proliferation and Affects Survival in Esophageal Cancer Patients. Clin Cancer Res.2006, 12(24):7322-7328.
86. Watson DI, Wijnhoven BP, Michael MZ, Mayne GC, Hussey DJ. Hp24microRNA expression profiles in Barrett's oesophagus. ANZ J Surg.2007,77(Suppl):A45.
87. Ohtal M, Mimoril K, Fukuyoshi Y, et al.Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer. British Journal of Cancer.2008,98,410-417.
88. Feber A, Xi LQ, Luketich JD, et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg.2008,135:255-260.
89. Guo Y, Chen ZL,Zhang L. Distinctive MicroRNA Profiles Relating to Patient Survival in Esophageal Squamous Cell Carcinoma Cancer Res.2008,68:(1):26-33.
2. Wang GQ, Jiao GG, Chang FB, et al. Long-term results of operation for 420 patients with early squamous cell esophageal carcinoma discovered by screening. Ann Thorac Surg.2004,77(5):1740-1744.
3. Ponec RJ, Kimmey MB. Endoscopic therapy of esophageal cancer. Surg Clin North Am.1997,77:1197-1217.
4. Nakajima Y. Nagai K, Miyake S, et al. Evaluation of an indicator for lynphnode metastasis of esophageal squamous cell carcinoma invading the submucosal layer. Jpn. J Cancer Res.2002,93:305-312.
5. Yanai H. Harada T, Okamoto T, et al. Prognostic value and interobserver agreement of endoscopic ultrasongraphy for superficial squmous cell carcinoma of the esophagus:a prospective study. Int J Gastrointest Cancer.2003,34(1):1-8.
6. Araki K, Ohno S, Egashira A. et al. Pathologic features of superficial esophageal squmous cell carcinoma with lymph node and distal metastasis. Cancer.2002, 94(2):570-575.
7. Herbst RS, Lippman SM. Molecular signatures of lung cancer-to ward personalized therapy. N Eng J Med.2007,356(1):76-78.
8. Kallioniemi A, Kallioniemi OP, Sudar D, etal. Comparative genomic hibridization for molecular cytogenetic analysis of solid tumors.Science,1992,258:818-821.
9. Lerman MI, Minna JD, et al. Tumor suppressor genes on chromosone3p involved in the patho-genesis of lung and other cancers. oncogene,2002,21(45):6915-6935.
10. Wu MS, Chang MC,Huang SP, et al. Correlation of histologic subtypes and replication error phenotype with Comparative genomich ybridization in gastric cancer.Genes Chromosones Cancer,2001,30(1):80-86.
11. DeAngelis PM, Stokke T, Beigi M, etal.Prognostic significance of recurrent chromosome alaberrations detected By comparative genomic hybridization in sporadic colorectal cancer. Int J Colorectal Dis,2001,16(1):38-45.
12. Pestova E, Wilber K, King W. Microarray based CGH in cancer.Methods Mol Med, 2004,97:355-375.
13. Su M, Chin SF, Li XY, et al. Comparative genomic hybridization of esophageal adenocarcinoma and squamous cell carcinoma cell lines. Dis Esophagus.2006, 19:10-14.
14. Sugimoto T, Arai M, Shimada H, et al. Integrated analysis of expression and genome alteration reveals putative amplified target genes in esophageal cancer. Oncol Rep.2007,18:465-472.
15. Kuwano H, Kato H, Miyazaki T, et al. Genetic alterations in esophageal cancer. Surg Today.2005,35:7-18.
16. Wu YP, Yang YL, Yang GZ, et al. Identification of chromosome aberrations in esophageal cancer cell line KYSE180 by multicolor fluorescence in situ hybridization. Cancer Genet Cytogenet.2006,170:102-107.
17. Marilanda FB, Ana ES, Marileila VG Genomic imbalances in esophageal squamous cell-carcinoma identified by molecular cytogenetic techniques. Genet-Mol. Biol., ahead of print Epub Apr 02,2010.
18.张旭,朱志华,林鹏等。食管不典型增生和早期食管鳞癌全基因组的变化特征分析。中华医学杂志,2008 Oct 14；88(37)：2636-2641.
19. Qin YR, Wang LD, Dora K, et al.Genomic changes in primary lesion and lymph node metastases of esophageal squamous cell carcinoma. Ai Zheng,2005, 24:1048-1053.
20. Qin YR, Wang LD, Kwong D, et al. Comparative genomic hybridization:The profile of chromosomal imbalances in esophageal squamous cell carcinoma. Zhonghua Bing Li Xue Za Zhi.2005,34:80-83.
21. Qin YR, Wang LD, Fan ZM, et al. Comparative genomic hybridization analysis of genetic aberrations associated with development of esophageal squamous cell carcinoma in Henan, China. World J Gastroenterol.2008,14:1828-1835.
22. Carneiro A, Isinger A, Karlsson A, et al.Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer. BMC Cancer,2008,8:98-107.
23. Wang LD, Qin YR, Fan ZM, et al. Comparative genomic hybridization:Comparison between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-incidence area for both cancers in Henan, northern China. Dis Esophagus.2006,19:459-467.
24. Yen CC, Chen YJ, Chen JT, et al. Comparative genomic hybridization of esophageal squamous cell carcinoma:correlations between chromosomal aberrations and disease progression/prognosis. Cancer,2001,92(10):2769-2777.
25. Ueno T, Tangoku A, Yoshino S, et al. Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma. Clin Cancer Res,2003 Nov 1,9 (14):5137-5141.
26. Ueno T, Tangoku A, Yoshino S, et al. Gain of 5p15 detected by comparative genomic hybridization as an independent marker of poor prognosis in patients with esophageal squamous cell carcinoma. Clin Cancer Res,2002,8:526-533.
27. Fujita Y, Sakakura C, Shimomura K, et al. Chromosome arm 20q gains and other genomic alterations in esophageal squamous cell carcinoma, as analyzed by comparative genomic hybridization and fluorescence in situ hybridization. Hepatogastroenterology.2003,50:1857-1863.
28. Xu FP, Xie D, Wen JM, et al. SRC-3/AIB1 protein and gene amplification levels in human esophageal squamous cell carcinomas. Cancer Lett.2007,245:69-74.
29. Shay JW, Wright WE. Implications of mapping the human telomerase gene (hTERT) as the most distal gene on chromosome 5p.Neoplasia,2000,2:195-201.
30. Bieche I, Nogues C, Paradis V et al. Quantitation of hTERT gene expression in sporadic breast tumors with a real-time reverse transcription-polymerase chain reaction assay. Clin Cancer Res,2000:452-459.
31. Komiya T, Kawase I, Nitia T ei al. Prognostic significance of hTERT expression in non-small cell lung cancer. Int. J. Oncol,2000,16:1173-1177.
32. Akervall JA. Michalides RJ. Mineta H, et al. Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclinD1 overexpression. Cancer,1997,79:380-389.
33. Mandard AM, Hainaut P, Hollstein M. Genetic steps in the development of squamous cell carcinoma of the esophagus. Mutat Res,2000,462:335-342.
34. Bockmuhl U, Schluns K, Kuchler I, et al. Genetic imbalances with impact on survival in head and neck cancer patients. Am. J. Pathol,2000,157:369-375.
35. Rodrigo JP, Garcia LA, Ramos S, et al. EMS1 gene amplification correlates with poor prognosis in squamous cell carcinomas of the head and neck. Clin Cancer Res, 2000,6:3177-3182.
36. Sunpaweravong P, Sunpaweravong S, Puttawibul P, et al. Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res.2005,131:111-119.
37. Naohide K, Masato H, Kuniko O, et al. Expression of TMEFF1 mRNA in the mouse central nervous system precise exam ination and comparative studies of TMEFF1 and TMEFF2. Mol Bra Res,2001,86:48—55.
38. Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet,1999,21: 163-167.
39. Matthias PA, Ebert W, Suzanne H. et al. Hypermethylation of the TPEF/HPP1 gene in primary and metastatic colorectal canaers.Neoplasia,2005,7:771—778.
40. Field JK, Liloglou T, Warrak S, et al.Methylation discriminators in NSCLC idntified by a microarray based approach.Int J Oncol.2005,27(1):105-111.
41. Kim BH, Cho NY, Shin SH, et al.CpG island hypermethylation and repetitive DNA hypomethylation in pre malignant lesion of extrahepatic cholangiocarcinoma. Virchows Arch.2009,455(4):343-351.
42. Smith E, De Young NJ, Pavey SJ,et al. Similarity of aberrant DNA methylation in Barre's esophagus and esophageal adenocarcinoma. Mol Cancer.2008, (7) 75.
43. Tsunoda S, Smith E, De Young NJ, et al. Methylation of CLDN6, FBN2, RBP1,RBP4, TFP12, and TMEFF2 in esophageal squamous cell carcinoma. Oncol Rep.2009,21(4):1067-1073.
44. Nooij-wan Dalen AG, Van Dongen GA, Smeets SJ, et al. Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K included, as molecular markers for head-and-neck squamous cell carcinoma. Int J Cancer,2003,103 (6):768-774.
45. Choi SH, Kong HK, Park SY, et al. Metastatic effect of LY-6K gene in breast cancer cells. Int J Oncol.2009,35(3):601-607.
46. Ishikawa N, Takano A, Yasui W, et al. Cancer-Testis Antigen Lymphocyte Antigen 6 Complex Locus K Is a Serologic Biomarker and a Therapeutic Target for Lung and Esophageal Carcinomas.Cancer Res.2007,67(24):11601-11611.
47. Ferdinandusse S,Denis S,Llst L,et al.Subcellular localization and physiological role of a-methylacyl-CoA racemase.J Lipid Res,2000,4(1):1890-1896.
48. Cuebas DA,Phillips C,Schmitz W,et al.The role of a-methlyaclyl-CoA racemase in bile acid synthesis J Biochem,2002,36(3):801-807.
49. Zhou M, Chinnaiyan AM, Kleer CG, et al.Alpha-methylacyl-CoA racemase:a novel tumor marker over-expressed in several human cancers and their precursor lesions.Surg Patho,2002,26:926-931.
50. Liu W, Caqle PT, Botero RC, et al.Significance of overexpression of alpha methylacyl-coenzyme A racemase in hepatocellular carcinoma. J Exp Clin Cancer Res.2008,15; 27:2.
51. Witkiewicz AK, Varambally S, Shen R,et al. Alpha-methylacyl-CoA racemase protein expression is associated with the degree of differentiation in breast cancer using quantitative image analysis. Cancer Epidemiol Biomarkes Prev.2005, 14(6):1418-1423.
52. Jiang Z, Wu CL, Woda, BA, et al. Alpha-methylacyl-CoA racemase:a multi-institutional study of a new prostate cancer marker. Histopathology.2004, 45(3):218-225.
53. Shi XY, Bhaqwandeen B, Leong AS. P16, cyclin D1, and AMACR as markers for
desplasia in Barrett esophagus. Appl Immunohistchem Mol Morphol.2008, 16(5):447-452.
54. Scheil BS, Lorenz D, Ell C, et al. expression of alpha-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett's esophagus. Mod Pathol.2008,21(8):961-967.
55. Ullrich A, Schlessinger J.Signal transduction by receptors with tyrosine kinase activity. Cell,1990,61(2):203-212.
56:Yue Y, Widmer DA, Halladay AK, et al. Specification of distinct dopaminergic neural pathways:roles of the Eph family receptor EphB1 and ligand ephrin-B2. J Neurosci.1999,19(6):2090-101.
57. Huynh DU, Vindis C, Liu H, et al.Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis. J Cell Sci.2002, 115(15):3073-81.
58. Sheng Z. Wang J, Dong Y. et al. EphBl is underexpressed in poorly differentiated colorectal cancers. Pathobiology.2008,75(5):274-280.
59. Wang JD, Dong YC, Sheng Z, et al. Loss of expression of EphBl protein in gastric carcinoma associated with invasion and metastasis.Oncology.2007,73(3-4):238-245.
60. Hu N, Wang CY, Hu Y, et al. Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array. Cancer Res.2005,65(7):2542-2546.
61. Chan KY, Lai PB, Squire JA, et al. Positionnal expression proiling indicates genes in deletion hotspots of hepatocellular carcinoma. Mod Pathol.2006,19(12):1546-1554.
62. Zhu WL, Fan BL, Liu DL, et al. Abnomal expression of fibrinogen gamma (FGG) and palsma level of fibrinogen in patients with hepatocellular carcinoma. J Thromb Haemost.2008,6(1):176-1783.
63. Sahni A, Simpson-Haidaris PJ, Sahni SK, et al. Fibrinogen synthesized by cancer cells auhments the proliferative effect of fibroblast growth factor-2 (FGF-2). J Thromb Haemost.2008,6(1):174-175.
1. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.Cell.1993,75(5):843-854.
2. Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature.2000,403(6772):901-906.
3. Brennecke J, Hipfner DR, Stark A, et al. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell.2003,113(1):25-36.
4. Xu P, Vernooy SY, Guo M, et al. The Drosophila microRNA mir-14 suppresses cell death and is required for normal fatmetabolism. CurrBiol.2003,13(9):790-795.
5. Dostie J, Mourelatos Z,Yang M, et al. Numerous microRNPs in neuronal cells containing novel microRNPs. RNA.2003,9(2):180-186.
6. Chen CZ, Li L, Lodish HF, et al. MicroRNAs modulate hemato-poietic lineage differentiation. Science.2004,303(5654):83-86.
7. Calin GA, Sevignani C, Dumitru CD,et al.Human mcroRNA genes are frequently located at fragile sites and genomic regions involved in cancers.Proc Natl Acad Sci USA.2004,101(9):2999-3004.
8. He L, Thomson JM, Hemannm T, etal.A microRNA poly-cistron as a potential human oncogene. Nature.2005,435:828-833.
9. O'Donnell KA, Wentzel EA, Zeller KI, et al.c-Myc-regulated microRNAs modulate E2F1 expression. Nature.2005,435(7043):839-843.
10. Monik AW, Kerstin B, et al. High expression of precursor microRNA-15/BICRNA in children with Burkitt lym-phoma.Genes, Chromosomes&Cancer.2004,39:167-169.
11. Eisp S, Tam W, Sun L, et al. A ccumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA.2005,102(10):3627-3632.
12. Voorhoeve PM, Agami R. The tumor-suppressive functions of the human INK4A locus. Cancer Cell.2003,4(4):311-319.
13. Takamizawa J, KonishiH, YanagisawaK, etal. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res.2004,64(11):3753-3756.
14. Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family.Cell 2005.120(5):635-647.
15. Cimmino A, Calin GA, Fabbri M, et al miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA.2005,102(39):13944-13949.
16. Karube Y, Tanaka H, Osaka H, et al. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci.2005,96(2):111-115.
17. Omoto S, Fujii YR. Regulation ofhuman immunodeficiency virusl transcription by nefmicroRNA. J GenViro.2005,86(Pt3):751-755.
18. Peeffer S, Zavolan M, Grosser FA, et al. Identification Of virus-encoded microRNAs. Science.2004,304:734-736.
19. Lu J, Getz G, Miska EA,et al. MicroRNA expression profiles classify human cancers. Nature.2005,435 (7043):834-838.
20. Calin GA, Ferracin M, Cmi Mino A, et al. A microRNA signature associatedwith prognosis and progression in chron-ic lymphocytic leukemia. N Eng J Med.2005, 353(17):1793-1801.
21. lorio MV, Ferracin M, Liu CG,et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res.2005,65(16):7065-7070.
22. Feber A, Xi L, Luketich JD, et al.MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg.2008,135(2):255-260.
23. Guo Y, Chen Z, Zhang L, et al. Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res.2008; 68(1):26-33.
24. Lee KH, Goan YG, Hsiao M, et al.microRNA-373(miR-373)post-transcriptionally regulates large tumor suppressor, homolog2(LATS2) and stimulates proliferation in human esophageal cancer.Exp Cell Res.2009,315(15):2529-2538.
25. Hiyoshi Y. Kamohara H. Karashima R. et al.. MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clin Cancer Res. 2009,15(6):1915-1922.
26. Hu Y, Correa AM, Hoque A, et al. prognostic significance of differentially expressed miRNAs in esophageal cancer. Int J Cancer.2010 Mar 22.[Epub ahead of print] 30e 16-22.
27. Oqawa R, Ishiquro H, Kuwabara Y, et al. expression profiling of micro-RNAs in human esophageal squmous cell carcinoma using RT-PCR. Med Mol Morphol.2009, 42(2):102-109.
28. He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature.2005,435(7043):828-833.
29. Ventura A, Young AG, Winslow MM, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008,132(5):875-886.
30. Koralov SB, Muljo SA, Galler GR, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell.2008,132(5):860-874.
31. Lu Y, Thomson JM, Wong HY, et al. Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol.2007,310(2):442-453.
32. Lu Y, Okubo T, Rawlins E, et al. Epithelial progenitor cells of the embryonic lung and the role of microRNAs in their proliferation. Proc Am Thorac Soc.2008,5(3): 300-304.
33. Suarez Y, Fernandez-hernando C, Yu J, et al. Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci USA.2008, 105(37):14082-14087.
34. Wang Q, Li YC, Wang J, et al. miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci USA.2008,105(8):2889-2894.
35. O'Donnel KA, Wentzel EA, Zeller KI, et al. C-myc-regulated microRNAs modulate E2F1 expression. Proc Natl Acad Sci USA.2005,435(7043):839-843.
36. Rinaldi A, Poretti G, Kwee I, et al. Concomitant MYC and microRNA cluster miR-17-92 (C13orf25) amplification in human mantle cell lymphoma. Leuk Lymphoma.2007,48(2):410-412.
37. Kutay H, Bai S, Datta J, et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem.2006,99(3):671-678.
38. Gottardo F, Liu CG, Ferracin M, et al.Micro-RNA profiling in kidney and bladder cancers. Urol Oncol.2007,25(5):387-392.
39. Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA.2006,103(7): 2257-2261.
40. Ota A, Tagawa H, Karnan S, et al.Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res.2004,64(9):3087-3095.
41. Anzick SL, Kononen J, Walker RL, et al. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science.1997,277(5328):965-968.
42. Wang Y, Wu MC, Sham JS, et al.Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer.2002,95(11):2346-2352.
43. Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol.2006,26(21): 8191-8201.
44. Valastyan S, Reinhardt F, Benaich N et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell.2009,137,1032-1046.
45. Valastyan S, Benajch N, Chang A. et al. Concomitant suppression of three target genes can explain the impact of microRNA on metastasis. Genes Dev.2009, Nov 15; 23 (22):2592-7.
46. Bandres E, Cubedo E, Aqirre X, et al. Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. MOL Cancer.2006, Jul 19; 5:29.
47. Liu X, Sempere LF, Ouyang H, et al. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors, J Clin Invest.2010 Apr;120(40):1298-309.
1. Pasquinelli AE, Hunter S, Bracht J,et al. MicroRNAs:a developing story.Curr Opin Genet Dev.2005,15:200-205.
2. Harfe BD. MicroRNAs in vertebrate development. Curr Opin Genet Dev.2005, 15:410-415.
3. Carleton M, Cleary MA, Linsley PS,et al. MicroRNAs and cell cycle regulation. Cell Cycle.2007,6:2127-2132.
4. Garzon R, et al. MicroRNA expression and function in cancer. Trends Mol Med. 2006,12:580-587.
5. Wang E. MicroRNA, the putative molecular control for mid-life decline. Ageing Res Rev.2007,6:1-11.
6. Boehm M, Slack FJ. MicroRNA control of lifespan and metabolism.Cell Cycle. 2006,5:837-840.
7. Calin GA, Dumitru CD, Shimizu M et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA.2002,99:15524-15529.
8. Lee RC, Feinbaum RL, Ambros V, et al. The C.elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell.1993, 75:843-854.
9. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function.Cell. 2004,116:281-297.
10. Berezikov E, Guryev V, van de Belt J, et al. Phylogenetic shadowing and computational identification of human microRNA genes. Cell.2005,120:21-24.
11. Bentwich I, Avniel A, Karov Y, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet.2005,37:766-770.
12. Cho WC. OncomiRs:the discovery and progress of microRNAs in cancers. Molecular Cancer.2007,6:60-66.
13. Cowland JB, Hother C, Gronbaek K, et al. MicroRNAs and cancer. APMIS. Journal Compilation C.2007,115:1090-1106.
14. Lee Y, et al. MicroRNA genes are transcribed by RNA polymerase Ⅱ. EMBO J. 2004; 23:4051-4060.
15. Lin, S.L., Chang D., Ying S.Y. Asymmetry of intronic pre-miRNA structures in functional RISC assembly. Gene.2005,356,32-38.
16. Gregory RI, Chendrimada TP, Shiekhattar R. MicroRNA biogenesis:isolation and characterization of the microprocessor complex. Methods Mol Biol.2006,342:33-47.
17. Bohnsack, M.T., Czaplinski K., Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediatesn nuclear export of pre-miRNAs. RNA.2004, 10,185-191.
18. Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3? UTR evolution.Cell 2005,123:1133-1146.
19. Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs downregulate large numbers of targetmRNAs. Nature 2005, 433:769-73.
20. Pattanayak, D., Agarwal S., Sumathi, S., et al. Small but mighty RNA-mediated interference in plants. Indian J. Exp. Biol.2005,43,7-24.
21. Hutvagner, G. Small RNA asymmetry in RNAi:Function in RISC assembly and gene regulation. FEBS Lett.2005,579,5850-5857.
22. Carthew, R.W. Gene regulation by microRNAs. Curr. Opin.Genet. Dev.2006,16, 203-208.
23. Castoldi M, Schmidt S, Benes V, et al. A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA.2006,12:913-920.
24. Thomson JM, Parker J, Perou CM, et al. A custom microarray platform for analysis of micro RNA gene expression. Nat Methods.2004,1:47-53.
25. Kloosterman WP, Wienholds E, de Bruijn E, et al. In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes. Nat Methods.2005. 3:27-29.
26. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature.2005,435:834-838.
27. Jiang J, Lee EJ, Gusev Y, Schmittgen TD. Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res.2005, 33:5394-5403.
28. Aoife JL, Miller N, Roisin EM, et al. MicroRNAs as Prognostic Indicators and Therapeutic Targets:Potential Effect on Breast Cancer Management. Clin Cancer Res.2008,14:360-364.
29. Dalmay T. MicroRNAs and cancer. Journal of Internal Medicine.2008,263; 366-375.
30. Fabbri M, Croce CM, Calin GA. MicroRNAs. The Cancer Journal.2008, 14(1):1-6.
31. Feber A, Xi LQ, Luketich JD, et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg.2008,135:255-260.
32. Sassen S, Miska EA, Caldas C. MicroRNA-implications for cancer, Virchows Arch.2008,452:1-10.
33. Visone R, Petrocca F, Croce CM. Micro-RNAs in Gastrointestinal and Liver Disease. Gastroenterology.2008,135:1866-1876.
34. Kumar MS, Lu J, Mercer KL, et al. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet.2007,39:673-677.
35. Calin GA, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell.2007,12:215-229.
36. Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med.2005, 353:1793-1801.
37. Cimmino A, Calin GA, Fabbri M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA.2005,102:13944-13949.
38. Garzon R, Pichiorri F, Palumbo T, et al. MicroRNAgene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia. Oncogene. 2007,26:4148-4157.
39. Bottoni A, Piccin D, Tagliati F, et al. miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol.2005,204:280-285.
40. Bandres E, Cubedo E, Agirre X, ct al. Identification by realtime PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer.2006,5:29.
41. Akao Y, Nakagawa Y, Kitade Y, et al. Downregulation of microRNAs-143 and-145 in B-cell malignancies. Cancer Sci.2007,98:1914-1920.
42. Akao Y, Nakagawa Y, Naoe T. MicroRNA-143 and-145 in colon cancer. DNA Cell Biol.2007,26:311-320.
43. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep 2006,16:845-850.
44. Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene.2007, 26:5017-5022.
45. Chang TC, Wentzel EA, Kent OA, et al.Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell.2007, 26:745-752.
46. He L, He X, Lim LP, et al.A microRNA component of the p53 tumour suppressor network. Nature.2007,447:1130-1134.
47. Yanaihara N, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell.2006,9:189-198.
48. Johnson SM, et al. RAS is regulated by the let-7 microRNA family. Cell.2005, 120:635-647.
49. Akao Y, Nakagawa Y, Naoe T. let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull.2006,29:903-906.
50. Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science.2007,315:1576-1579.
51. Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev.2007,21:1025-1030.
52. Tam W, et al. Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis. J Virol.2002, 76:4275-4286.
53. Volinia S, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA.2006,103:2257-2261.
54. Eis PS, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA.2005,102:3627-3632.
55. Costinean S, Zanesi N, Pekarsky Y, et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E (mu)-miR155 transgenic mice. Proc Natl Acad Sci USA.2006,103:7024-7029.
56. Fulci V, Chiaretti S, Goldoni M, et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood.2007,109:4944-4951.
57. Roldo C, Missiaglia E, Hagan JP, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol.2006,24:4677-4684.
58. Gironella M, et al. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA.2007,104:16170-16175.
59. Iorio MV, Ferracin M, Liu CG et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005; 65:7065-7070.
60. Si ML, Zhu S, Wu H, et al. miR-21-mediated tumor growth. Oncogene,2007, 26:2799-2803.
61. Zhu S, Si ML, Wu H, Mo YY:MicroRNA-21 Targets the tumor suppressor gene Tropomyosin 1 (TPM1). J Biol Chem.2007,282:14328-14336.
62. Wu W, et al. MicroRNA and cancer:current status and prospective. Int J Cancer. 2007,120:953-960.
63. Hayashita Y, Osada H, Tatematsu Y et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65:9628-9632.
64. Matsubara H, Takeuchi T, Nishikawa E, et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene,2007,26:6099-6105
65. He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature,2005,435:828-833.
66. Venturini L, et al. Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34_ cells. Blood.2007,109:4399-4405.
67. O'Donnell KA, et al. c-Myc-regulated microRNAs modulate E2F1 expression. Nature.2005,435:839-843.
68. Felli N, et al. MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA.2005,102:18081-18086.
69. Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, Chiappetta G, Liu CG, Santoro M, Negrini M, Croce CM, Fusco A:MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer.2006, 13:497-508.
70. Ciafre SA, Galardi S, Mangiola A et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun.2005,334: 1351-1358.
71. Pavlidisa N, Fizazib K. Cancer of unknown primary (CUP). Crit Rev Oncol Hematol.2005,54:243-250.
72. Bloomston M, Frankel WL, Petrocca F, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA.2007,297:1901-1908.
73. Lee EJ, Gusev Y, Jiang J, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer.2007,120:1046-1054.
74. Ma L, Weinberg RA.Micromanagers of malignancy:role of microRNAs in regulating metastasis. Trends in Genetics.2008,24 (9):448-456.
75. Dews M, Homayouni A, Yu D et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet.2006,38:1060-1065.
76. Ma L, Teruya-Feldstein J, Weinberg RA.Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature.2007,449:682-688.
77. Mourad, P.D. et al. Why are systemic glioblastoma metastases rare? Systemic and cerebral growth of mouse glioblastoma. Surg.Neurol.2005.63:511-519.
78. Tavazoie, S.F. et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature.2008,451,147-152.
79. Budhu, A. et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology.2008,47:897-907.
80. Huang, Q. et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat. Cell Biol.2008,10:202-210.
81. Guo Y, Chen ZL,Zhang L. Distinctive MicroRNA Profiles Relating to Patient Survival in Esophageal Squamous Cell Carcinoma Cancer Res.2008,68:(1):26-33.
82. Visone R, Petrocca F, Croce CM. Micro-RNAs in Gastrointestinal and Liver Disease. Gastroenterology.2008,135:1866-1876.
83. Selaru FM, Zou T, Xu Y, et al. Global gene expression profiling in Barrett's esophagus and esophageal cancer:a comparative analysis using cDNA microarrays. Oncogene.2002,21:475-478.
84. Helm J, Enkemann SA, Coppola D, Barthel JS, Kelley ST, Yeatman TJ. Dedifferentiation precedes invasion in the progression from Barrett's metaplasia. Cancer Res.2008,68:(1):26-33.
85. Sugito N, Ishiguro H, Kuwabara Y et al. RNASEN Regulates Cell Proliferation and Affects Survival in Esophageal Cancer Patients. Clin Cancer Res.2006, 12(24):7322-7328.
86. Watson DI, Wijnhoven BP, Michael MZ, Mayne GC, Hussey DJ. Hp24microRNA expression profiles in Barrett's oesophagus. ANZ J Surg.2007,77(Suppl):A45.
87. Ohtal M, Mimoril K, Fukuyoshi Y, et al.Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer. British Journal of Cancer.2008,98,410-417.
88. Feber A, Xi LQ, Luketich JD, et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg.2008,135:255-260.
89. Guo Y, Chen ZL,Zhang L. Distinctive MicroRNA Profiles Relating to Patient Survival in Esophageal Squamous Cell Carcinoma Cancer Res.2008,68:(1):26-33.