MicroRNA-449a在肺癌细胞中的功能及其分子机制
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摘要
肺癌是全球范围内因癌症导致死亡最重要的原因,在我国,肺癌的发生率和死亡率都呈明显上升的趋势,其5年生存率只有20%左右。其主要原因是大多数肺癌患者在确诊时癌细胞已经发生转移。microRNAs(miRNAs)是一类存在于真核生物中,内源性的,长度约为22nt的小分子RNA,通过靶向mRNA的3'UTR结合序列,降解mRNA或抑制其翻译。miRNA通过参与基因转录后水平调控,在个体发育,细胞增殖,分化及凋亡等生命过程中起重要作用。越来越多的证据表明,1miRNA的表达和功能失调与肿瘤的发生,发展密切相关,在肿瘤中发挥着类似于癌基因或抑癌基因的功能。
MicroRNA-449a (miR-449a)的表达下调常见于多种肿瘤中,但在肺癌中的生物学功能尚未明确。在本论文中,我们通过一系列的细胞和分子生物学实验技术,研究了miR-449a在肺癌中的表达及生理,病理学作用。首先我们利用qRT-PCR的方法检测了miR-449a在156例肺癌组织(主要是腺癌)以及肺癌细胞系中的表达,结果发现miR-449a在肺癌组织及肺癌细胞系中表达明显下调。同时我们采用x2分析miR-449a的表达水平与患者的性别,年龄,吸烟史,病理类型,复发情况,死亡情况等临床特征的相关性,结果显示miR-449a的表达与肺癌病人的性别,复发和死亡情况密切相关。为了进一步明确miR-449a的诊断价值,我们分析了miR-449a的表达和预后的关系,Kaplan-Meier生存分析显示,miR-449a低表达组病人生存时间要明显比高表达组病人短(p=0.019, log-rank test)。在体外miR-449a能明显降低肺癌细胞系的生长活力,抑制细胞的增殖,促进细胞的衰老和凋亡,而且能明显抑制肺癌细胞在小鼠体内成瘤的能力。双荧光报告基因系统,qRT-PCR和western blot实验表明,过表达lniR-449a能够降低E2F33'UTR报告载体的荧光素酶活性,抑制E2F3mRNA和蛋白水平的表达,并且miR-449a能明显降低E2F3基因的转录激活活性,证明E2F3是miR-449a的一个直接的作用靶点。在肺癌细胞中利用si-RNA沉默E2F3的表达可产生和过表达miR-449a类似的细胞周期阻滞和细胞衰老现象,而过表达E2F3,则可以恢复由过表达miR-449a所引起的细胞活力的下降。此外,miR-449a也显著抑制了CCND1,CDK6蛋白的表达。本论文的研究结果揭示了miR-449a在肺癌发生过程中和细胞周期调控中的重要作用,提示miR-449a可以作为肺癌诊断和预后的一个重要的标志物,并且在肺癌的治疗中具有潜在的应用价值。
Lung cancer is the leading cause of cancer deaths worldwide, and has a rapidly increasing incidence and mortality in our country. Five-year survival rate of lung cancer is only20%. A major reason for poor outcomes in the lung cancer patients is that have spread beyond the primary site at the time of diagnosis. MicroRNAs (miRNAs) are endogenous, small noncoding RNAs about22nt long that are found in eukaryotes, and can regulate the translation or degradation of messenger RNA (mRNA) through pairing with complementary nucleotide sequences in the3'-untranslated region (3'-UTR) of target mRNA. miRNA negative regulates the gene expression in a posttranscriptional manner. To date, miRNAs have been involved in a wide range of cellular processes, such as development, cellular proliferation, differentiation, and apoptosis. Recently, growing evidence has indicated that deregulation of miRNAs contributes to tumorigenesis. miRNAs can function as oncogenes or tumor suppressors involved in cancer developmemt.
Dysregulation of microRNA-449a (miR-449a) has been detected in various types of human cancers. However, the biological function of miR-449a in lung tumorigenesis remains largely unclear. In the present study, we aimed to identify the expression and pathophysiologic significance of miR-449a in lung cancer. Using quantitative RT-PCR (qRT-PCR), we analyzed the expression of miR-449a in156human lung cancer tissues (predominantly adenocarcinoma) and lung cancer cell lines. Our results showed that compared with paired normal tissues, miR-449a expression was significantly downregulated in156lung cancer tissues (p<0.001) and the lung cancer cell lines examined. We also investigated whether miR-449a downregulation is related to clinicopathological features of lung cancer patients, including sex, age, smoking history, histologic type, recurrence and death.χ2tests revealed a significant relationship between low miR-449a expression and patient sex, recurrence and death. To determine whether the expression of mature miR-449a was related to the prognosis of lung cancer patients, miR-449a was used for further survival analysis. Kaplan-Meier survival analysis revealed that lung cancer patients with reduced miR-449a expression had shorter survival than did patients with high miR-449a expression (p=0.019by log-rank test). The transient introduction of miR-449a into lung cancer cells caused cell cycle arrest, cell senescence, and cell apoptosis in vitro. miR-449a also suppressed tumor formation in vivo in nude mice. Further studies (Luciferase reporter assay, qRT-PCR, western-blot) revealed that overexpression of miR-449a significantly suppressed the luciferase activity of reporter plasmids containing the3'-untranslated sequence of E2F3, and also decreased E2F3mRNA and protein levels. Moreover, introduction of miR-449a significantly repressed the transactivation of E2F3. These results suggested that E2F3is a direct target of miR-449a. Moreover, silencing of E2F3by siRNA also inhibited cell proliferation and induced a senescent phenotype in lung cancer cells. E2F3overexpression rescued the suppression of cell viability caused by miR-449a. Overexpression of miR-449a also significantly decreased protein levels of CCND1and CDK.6. Taken together, our results suggest that miR-449a plays an important role in the tumorigenesis of lung cancer and might be a predictor of cancer recurrence and survival in lung cancer patients.It might have the potential therapeutic applications.
MicroRNA-449a (miR-449a)的表达下调常见于多种肿瘤中,但在肺癌中的生物学功能尚未明确。在本论文中,我们通过一系列的细胞和分子生物学实验技术,研究了miR-449a在肺癌中的表达及生理,病理学作用。首先我们利用qRT-PCR的方法检测了miR-449a在156例肺癌组织(主要是腺癌)以及肺癌细胞系中的表达,结果发现miR-449a在肺癌组织及肺癌细胞系中表达明显下调。同时我们采用x2分析miR-449a的表达水平与患者的性别,年龄,吸烟史,病理类型,复发情况,死亡情况等临床特征的相关性,结果显示miR-449a的表达与肺癌病人的性别,复发和死亡情况密切相关。为了进一步明确miR-449a的诊断价值,我们分析了miR-449a的表达和预后的关系,Kaplan-Meier生存分析显示,miR-449a低表达组病人生存时间要明显比高表达组病人短(p=0.019, log-rank test)。在体外miR-449a能明显降低肺癌细胞系的生长活力,抑制细胞的增殖,促进细胞的衰老和凋亡,而且能明显抑制肺癌细胞在小鼠体内成瘤的能力。双荧光报告基因系统,qRT-PCR和western blot实验表明,过表达lniR-449a能够降低E2F33'UTR报告载体的荧光素酶活性,抑制E2F3mRNA和蛋白水平的表达,并且miR-449a能明显降低E2F3基因的转录激活活性,证明E2F3是miR-449a的一个直接的作用靶点。在肺癌细胞中利用si-RNA沉默E2F3的表达可产生和过表达miR-449a类似的细胞周期阻滞和细胞衰老现象,而过表达E2F3,则可以恢复由过表达miR-449a所引起的细胞活力的下降。此外,miR-449a也显著抑制了CCND1,CDK6蛋白的表达。本论文的研究结果揭示了miR-449a在肺癌发生过程中和细胞周期调控中的重要作用,提示miR-449a可以作为肺癌诊断和预后的一个重要的标志物,并且在肺癌的治疗中具有潜在的应用价值。
Lung cancer is the leading cause of cancer deaths worldwide, and has a rapidly increasing incidence and mortality in our country. Five-year survival rate of lung cancer is only20%. A major reason for poor outcomes in the lung cancer patients is that have spread beyond the primary site at the time of diagnosis. MicroRNAs (miRNAs) are endogenous, small noncoding RNAs about22nt long that are found in eukaryotes, and can regulate the translation or degradation of messenger RNA (mRNA) through pairing with complementary nucleotide sequences in the3'-untranslated region (3'-UTR) of target mRNA. miRNA negative regulates the gene expression in a posttranscriptional manner. To date, miRNAs have been involved in a wide range of cellular processes, such as development, cellular proliferation, differentiation, and apoptosis. Recently, growing evidence has indicated that deregulation of miRNAs contributes to tumorigenesis. miRNAs can function as oncogenes or tumor suppressors involved in cancer developmemt.
Dysregulation of microRNA-449a (miR-449a) has been detected in various types of human cancers. However, the biological function of miR-449a in lung tumorigenesis remains largely unclear. In the present study, we aimed to identify the expression and pathophysiologic significance of miR-449a in lung cancer. Using quantitative RT-PCR (qRT-PCR), we analyzed the expression of miR-449a in156human lung cancer tissues (predominantly adenocarcinoma) and lung cancer cell lines. Our results showed that compared with paired normal tissues, miR-449a expression was significantly downregulated in156lung cancer tissues (p<0.001) and the lung cancer cell lines examined. We also investigated whether miR-449a downregulation is related to clinicopathological features of lung cancer patients, including sex, age, smoking history, histologic type, recurrence and death.χ2tests revealed a significant relationship between low miR-449a expression and patient sex, recurrence and death. To determine whether the expression of mature miR-449a was related to the prognosis of lung cancer patients, miR-449a was used for further survival analysis. Kaplan-Meier survival analysis revealed that lung cancer patients with reduced miR-449a expression had shorter survival than did patients with high miR-449a expression (p=0.019by log-rank test). The transient introduction of miR-449a into lung cancer cells caused cell cycle arrest, cell senescence, and cell apoptosis in vitro. miR-449a also suppressed tumor formation in vivo in nude mice. Further studies (Luciferase reporter assay, qRT-PCR, western-blot) revealed that overexpression of miR-449a significantly suppressed the luciferase activity of reporter plasmids containing the3'-untranslated sequence of E2F3, and also decreased E2F3mRNA and protein levels. Moreover, introduction of miR-449a significantly repressed the transactivation of E2F3. These results suggested that E2F3is a direct target of miR-449a. Moreover, silencing of E2F3by siRNA also inhibited cell proliferation and induced a senescent phenotype in lung cancer cells. E2F3overexpression rescued the suppression of cell viability caused by miR-449a. Overexpression of miR-449a also significantly decreased protein levels of CCND1and CDK.6. Taken together, our results suggest that miR-449a plays an important role in the tumorigenesis of lung cancer and might be a predictor of cancer recurrence and survival in lung cancer patients.It might have the potential therapeutic applications.
引文
Akao Y, Nakagawa Y and Naoe T.2007. MicroRNA-143 and-145 in colon cancer[J]. DNA Cell Biol,26:311-320.
Ambros V.1989. A Hierarchy of Regulatory Genes Controls a Larva-to-Adult Developmental Switch in C-Elegans[J]. Cell,57:49-57.
Ambros V, Bartel B, Bartel DP, et al.2003. A uniform system for microRNA annotation[J]. RNA, 9:277-279.
Asangani IA, Rasheed SA, Nikolova DA, et al.2008. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer[J].Oncogene,27:2128-2136.
Bandi N and Vassella E.2011. miR-34a and miR-15a/16 are co-regulated in non-small cell lung cancer and control cell cycle progression in a synergistic and Rb-dependent manner[J]. Mol Cancer,10.
Bandres E, Bitarte N, Arias F, et al.2009. microRNA-451 Regulates Macrophage Migration Inhibitory Factor Production and Proliferation of Gastrointestinal Cancer Cells[J]. Clinical Cancer Research,15:2281-2290.
Bartel DP.2004. MicroRNAs:Genomics, biogenesis, mechanism, and function[J]. Cell, 116:281-297.
Bartel DP.2007. MicroRNAs:Genomics, biogenesis, mechanism, and function (Reprinted from Cell,vol 116, pg 281-297,2004)[J]. Cell,131:11-29.
Bartel DP.2009. MicroRNAs:Target Recognition and Regulatory Functions[J]. Cell, 136:215-233.
Behm-Ansmant I, Rehwinkel J, Doerks T, et al.2006. mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes[J]. Genes Dev,20:1885-1898.
Bernstein E, Caudy AA, Hammond SM, et al.2001. Role for a bidentate ribonuclease in the initiation step of RNA interference[J]. Nature,409:363-366.
Boffetta P and Nyberg F.2003. Contribution of environmental factors to cancer risk[J]. British Medical Bulletin,68:71-94.
Bohnsack MT, Czaplinski K and Gorlich D.2004. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs[J]. RNA,10:185-191.
Bommer GT, Gerin I, Feng Y, et al.2007. p53-mediated activation of miRNA34 candidate tumor-suppressor genes[J]. Curr Biol,17:1298-1307.
Borchert GM, Lanier W and Davidson BL.2006. RNA polymerase III transcribes human microRNAs[J]. Nature Structural & Molecular Biology,13:1097-1101.
Bou Kheir T, Futoma-Kazmierczak E, Jacobsen A, et al.2011. miR-449 inhibits cell proliferation and is down-regulated in gastric cancer[J]. Molecular Cancer,10:29.
Brooker R, Hozumi K and Lewis J.2006. Notch ligands with contrasting functions:Jagged1 and Deltal in the mouse inner ear[J]. Development,133:1277-1286.
Calin GA.2006. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia (vol 353, pg 1793,2005)[J]. New England Journal of Medicine, 355:533-533.
Calin GA and Croce CM.2006. MicroRNA signatures in human cancers[J]. Nature Reviews Cancer,6:857-866.
Calin GA, Dumitru CD, Shimizu M, et al.2002. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia[J]. Proceedings of the National Academy of Sciences of the United States of America, 99:15524-15529.
Calin GA, Ferracin M, Cimmino A, et al.2005. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia[J]. New England Journal of Medicine, 353:1793-1801.
Calin GA, Sevignani C, Dan Dumitru C, et al.2004. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers[J]. Proceedings of the National Academy of Sciences of the United States of America,101:2999-3004.
Campisi J.2005. Senescent cells, tumor suppression, and organismal aging:Good citizens, bad neighbors[J]. Cell,120:513-522.
Capuano M, Iaffaldano L, Tinto N, et al.2011. MicroRNA-449a overexpression, reduced NOTCH1 signals and scarce goblet cells characterize the small intestine of celiac patients[J]. PLoS One,6:e29094.
Carmell MA and Hannon GJ.2004. RNase III enzymes and the initiation of gene silencing[J]. Nat Struct Mol Biol,11:214-218.
Carthew RW and Sontheimer EJ.2009. Origins and Mechanisms of miRNAs and siRNAs[J]. Cell, 136:642-655.
Chan JA, Krichevsky AM and Kosik KS.2005. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells[J]. Cancer Res,65:6029-6033.
Chang TC, Wentzel EA, Kent OA, et al.2007a. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis[J]. Mol Cell,26:745-752.
Chang TC, Wentzel EA, Kent OA, et al.2007b. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis[J]. Mol Cell,26:745-752.
Chen CZ, Li L, Lodish HF, et al.2004. MicroRNAs modulate hematopoietic lineage differentiation[J]. Science,303:83-86.
Chen H, Lin YW, Mao YQ, et al.2012. MicroRNA-449a acts as a tumor suppressor in human bladder cancer through the regulation of pocket proteins[J]. Cancer Letters,320:40-47.
Chen WH, Bochmann F and Sun Y.2007. Effects of work related confounders on the association between silica exposure and lung cancer:a nested case-control study among Chinese miners and pottery workers[J]. International Archives of Occupational and Environmental Health, 80:320-326.
Chen YC, Davidson B, Cheng CC, et al.2005. Identification and characterization of membralin, a novel tumor-associated gene, in ovarian carcinoma[J]. Biochim Biophys Acta,1730:96-102.
Chendrimada TP, Finn KJ, Ji XJ, et al.2007. MicroRNA silencing through RISC recruitment of eIF6[J]. Nature,447:823-U821.
Cheng YW, Chiou HL, Sheu GT, et al.2001. The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women[J]. Cancer Res, 61:2799-2803.
Chiu HF, Cheng MH, Tsai SS, et al.2006. Outdoor air pollution and female lung cancer in Taiwan[J]. Inhalation Toxicology,18:1025-1031.
Choi N, Baumann M, Flentjie M, et al.2001. Predictive factors in radiotherapy for non-small cell lung cancer:present status[J]. Lung Cancer,31:43-56.
Ciafre SA, Galardi S, Mangiola A, et al.2005. Extensive modulation of a set of microRNAs in primary glioblastoma[J]. Biochem Biophys Res Commun,334:1351-1358.
Cocco P, Rice CH, Chen JQ, et al.2001. Lung cancer risk, silica exposure, and silicosis in Chinese mines and pottery factories:The modifying role of other workplace lung carcinogens[J]. Am J Ind Med,40:674-682.
Coieman WB and Tsongalis GJ.2006. Molecular mechanisms of human carcinogenesis[J]. EXS:321-349.
Collado M, Blasco MA and Serrano M.2007. Cellular senescence in cancer and aging[J]. Cell, 130:223-233.
Cooper CS, Nicholson AG,Foster C, et al.2006. Nuclear overexpression of the E2F3 transcription factor in human lung cancer[J]. Lung Cancer,54:155-162.
Corsten MF, Miranda R, Kasmieh R, et al.2007. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas[J]. Cancer Res,67:8994-9000.
Costa RH, Kalinichenko VV, Holterman AX, et al.2003. Transcription factors in liver development, differentiation, and regeneration[J]. Hepatology,38:1331-1347.
Cullen BR.2004. Transcription and processing of human microRNA precursors[J]. Mol Cell, 16:861-865.
Donnem T, Eklo K, Berg T, et al.2011. Prognostic Impact of MiR-155 in Non-Small Cell Lung Cancer Evaluated by in Situ Hybridization[J]. Journal of Translational Medicine,9.
Duan RH, Pak CH and Jin P.2007. Single nucleotide polymorphism associated with mature miR-125 a alters the processing o f pri-miRNA [J]. Human Molecular Genetics,16:1124-1131.
Dutta KK, Zhong Y, Liu YT, et al.2007. Association of microRNA-34a overexpression with proliferation is cell type-dependent[J]. Cancer Science,98:1845-1852.
Eberharter A and Becker PB.2002. Histone acetylation:a switch between repressive and permissive chromatin-Second in review series on chromatin dynamics[J]. Embo Reports, 3:224-229.
Eis PS, Tam W, Sun LP, et al.2005. Accumulation of miR-155 and BIC RNA in human B cell lymphomas[J]. Proceedings of the National Academy of Sciences of the United States of America,102:3627-3632.
Erren TC, Morfeld P, Glende CB, et al.2007. Silica and lung cancer[J]. Epidemiology, 18:521-521.
Farazi TA, Juranek SA and Tuschl T.2008. The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members[J]. Development,135:1201-1214.
Feng SP, Cong SJ, Zhang X, et al.2011. MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells[J]. Nucleic Acids Res, 39:6669-6678.
Field RW, Krewski D, Lubin JH, et al.2006. An overview of the North American residential radon and lung cancer case-control studies[J]. J Toxicol Environ Health A,69:599-631.
Filipowicz W, Bhattacharyya SN and Sonenberg N.2008. Mechanisms of post-transcriptional regulation by microRNAs:are the answers in sight?[J]. Nature Reviews Genetics,9:102-114.
Fire A, Xu S, Montgomery MK, et al.1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans[J]. Nature,391:806-811.
Foster CS, Falconer A, Dodson AR, et al.2004. Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome[J]. Oncogene,23:5871-5879.
Fraga MF and Esteller M.2005. Towards the human cancer epigenome -A first draft of histone modifications[J]. Cell Cycle,4:1377-1381.
Friedman RC, Farh KKH, Burge CB, et al.2009. Most mammalian mRNAs are conserved targets of microRNAs[J]. Genome Research,19:92-105.
Frisch M, Biggar RJ, Engels EA, et al.2001. Association of cancer with AIDS-related immunosuppression in adults[J]. Jama-Journal of the American Medical Association, 285:1736-1745.
Galardi S, Mercatelli N, Giorda E, et al.2007. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1[J]. J Biol Chem,282:23716-23724.
Gallardo E, Navarro A, Vinolas N, et al.2009. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer[J]. Carcinogenesis,30:1903-1909.
Giraldez AJ, Mishima Y, Rihel J, et al.2006. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs[J]. Science,312:75-79.
Granville CA and Dennis PA.2005. An overview of lung cancer genomics and proteomics[J]. Am J Respir Cell Mol Biol,32:169-176.
Gregory RI, Yan KP, Amuthan G, et al.2004. The Microprocessor complex mediates the genesis of microRNAs[J]. Nature,432:235-240.
Grun D, Wang YL, Langenberger D, et al.2005. MicroRNA target predictions across seven Drosophila species and comparison to mammalian targets[J]. Plos Computational Biology, 1:51-66.
Guarnieri DJ and Dileone RJ.2008. MicroRNAs:A new class of gene regulators[J]. Annals of Medicine,40:197-208.
Gwizdek C, Ossareh-Nazari B, Brownawell AM, et al.2003. Exportin-5 mediates nuclear export of minihelix-containing RNAs[J]. J Biol Chem,278:5505-5508.
Han JJ, Lee Y, Yeom KH, et al.2004. The Drosha-DGCR8 complex in primary microRNA processing[J]. Genes Dev,18:3016-3027.
Harbour JW, Lai SL, Whangpeng J, et al.1988. Abnormalities in Structure and Expression of the Human Retinoblastoma Gene in Sclc[J]. Science,241:353-357.
Hayashita Y, Osada H, Tatematsu Y, et al.2005. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation[J]. Cancer Res, 65:9628-9632.
He H, Jazdzewski K, Li W, et al.2005a. The role of microRNA genes in papillary thyroid carcinoma[J]. Proc Natl Acad Sci U S A,102:19075-19080.
He L, He X, Lim LP, et al.2007a. A microRNA component of the p53 tumour suppressor network[J]. Nature,447:1130-1134.
He L, He XY, Lim LP, et al.2007b. A microRNA component of the p53 tumour suppressor network[J]. Nature,447:1130-U1116.
He L, Thomson JM, Hemann MT, et al.2005b. A microRNA polycistron as a potential human oncogene[J]. Nature,435:828-833.
Hennekens CH, Buring JE, Manson JE, et al.1996. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease[J]. N Engl J Med,334:1145-1149.
Hoesel B, Bhujabal Z, Przemeck GK, et al.2010. Combination of in silico and in situ hybridisation approaches to identify potential Dill associated miRNAs during mouse embryogenesis[J]. Gene Expr Patterns,10:265-273.
Hornsby PJ.2007. Senescence as an anticancer mechanism[J]. Journal of Clinical Oncology, 25:1852-1857.
Hutvagner G and Simard MJ.2008. Argonaute proteins:key players in RNA silencing[J]. Nature Reviews Molecular Cell Biology,9:22-32.
Iorio MV, Ferracin M, Liu CG, et al.2005. MicroRNA gene expression deregulation in human breast cancer[J]. Cancer Res,65:7065-7070.
Ivan M.2008. The ongoing microRNA revolution and its impact in biology and medicine FOREWORD[J]. Journal of Cellular and Molecular Medicine,12:1425-1425.
Ivanovska I, Ball AS, Diaz RL, et al.2008. MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression[J]. Molecular and Cellular Biology, 28:2167-2174.
Jassem E and Jassem J.1996. [Mutation of gene p53 in lung cancer][J]. Pneumonol Alergol Pol, 64:5-10.
Jemal A, Bray F, Center MM, et al.2011. Global cancer stati sties [J]. CA Cancer J Clin,61:69-90.
Jeong HC, Kim EK, Lee JH, et al.2011. Aberrant expression of let-7a miRNA in the blood of non-small cell lung cancer patients[J]. Molecular Medicine Reports,4:383-387.
Johnson SM, Grosshans H, Shingara J, et al.2005. RAS is regulated by the let-7 MicroRNA family[J]. Cell,120:635-647.
Jones PA and Baylin SB.2002. The fundamental role of epigenetic events in cancer[J]. Nature Reviews Genetics,3:415-428.
Joseph B, Lewensohn R and Zhivotovsky B.2000. Role of apoptosis in the response of lung carcinomas to anti-cancer treatment[J]. Ann N Y Acad Sci,926:204-216.
Kaghad M, Bonnet H, Yang A, et al.1997. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers[J]. Cell,90:809-819.
Karube Y, Tanaka H, Osada H, et al.2005. Reduced expression of Dicer associated with poor prognosis in lung cancer patients[J]. Cancer Science,96:111-115.
Khvorova A, Reynolds A and Jayasena SD.2003. Functional siRNAs and miRNAs exhibit strand bias(vol 115, pg 209,2003)[J]. Cell,115:505-505.
Kiernan AE, Cordes R, Kopan R, et al.2005. The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear[J]. Development, 132:4353-4362.
Kim VN.2004. MicroRNA precursors in motion:exportin-5 mediates their nuclear export[J]. Trends in Cell Biology,14:156-159.
Kim VN, Han J and Siomi MC.2009. Biogenesis of small RNAs in animals[J]. Nat Rev Mol Cell Biol,10:126-139.
Kim YK and Kim VN.2007. Processing of intronic microRNAs[J]. Embo Journal,26:775-783.
Kiriakidou M, Tan GS, Lamprinaki S, et al.2007. An mRNA m7G cap binding-like motif within human Ago2 represses translation[J]. Cell,129:1141-1151.
Kluiver J, Poppema S, de Jong D, et al.2005. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas[J]. Journal of Pathology, 207:243-249.
Kluiver J, van den Berg A, de Jong D, et al.2007. Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma[J]. Oncogene,26:3769-3776.
Kong W, Yang H, He L, et al.2008. MicroRNA-155 Is Regulated by the Transforming Growth Factor beta/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA[J]. Molecular and Cellular Biology,28:6773-6784.
Kovesdi I, Reichel R and Nevins JR.1986. Identification of a Cellular Transcription Factor Involved in Ela Transactivation[J]. Cell,45:219-228.
Krutzfeldt J, Rajewsky N, Braich R, et al.2005. Silencing of microRNAs in vivo with 'antagomirs'[J]. Nature,438:685-689.
Lachet B.2006. Indoor radon and lung cancer[J]. Epidemiology,17:121; author reply 121-122.
Lagos-Quintana M, Rauhut R, Lendeckel W, et al.2001. Identification of novel genes coding for small expressed RNAs[J]. Science,294:853-858.
Lam WK, White NW and Chan-Yeung MM.2004. Lung cancer epidemiology and risk factors in Asia and Africa[J]. International Journal of Tuberculosis and Lung Disease,8:1045-1057.
Lau NC, Lim LP, Weinstein EG, et al.2001. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans[J]. Science,294:858-862.
Lawrie CH, Soneji S, Marafioti T, et al.2007. MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma[J]. International Journal of Cancer,121:1156-1161.
Lee RC and Ambros V.2001. An extensive class of small RNAs in Caenorhabditis elegans[J]. Science,294:862-864.
Lee RC, Feinbaum RL and Ambros V.1993. The C-Elegans Heterochronic Gene Lin-4 Encodes Small Rnas with Antisense Complementarity to Lin-14[J]. Cell,75:843-854.
Lee Y, Ahn C, Han JJ, et al.2003. The nuclear RNase Ⅲ Drosha initiates microRNA processing[J]. Nature,425:415-419.
Lee Y, Jeon K, Lee JT, et al.2002. MicroRNA maturation:stepwise processing and subcellular localization[J]. EMBO J,21:4663-4670.
Lee Y, Kim M, Han JJ, et al.2004. MicroRNA genes are transcribed by RNA polymerase Ⅱ[J]. Embo Journal,23:4051-4060.
Lee YS and Dutta A.2007. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene[J]. Genes Dev,21:1025-1030.
Lehmann U, Hasemeier B, Christgen M, et al.2008. Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer[J]. Journal of Pathology,214:17-24.
Leone G, DeGregori J, Yan Z, et al.1998. E2F3 activity is regulated during the cell cycle and is required for the induction of S phase[J]. Genes & Development,12:2120-2130.
Leone G, Sears R, Huang E, et al.2001. Myc requires distinct E2F activities to induce S phase and apoptosis[J]. Molecular Cell,8:105-113.
Lewis BP, Shih IH, Jones-Rhoades MW, et al.2003. Prediction of mammalian microRNA targets[J]. Cell,115:787-798.
Li AL and Mao L.2007. Evolution of plant microRNA gene families[J]. Cell Research, 17:212-218.
Liang Y.2008. An expression meta-analysis of predicted microRNA targets identifies a diagnostic signature for lung cancer[J]. BMC Med Genomics,1:61.
Liang Y, Ridzon D, Wong L, et al.2007. Characterization of microRNA expression profiles in normal human tissues[J]. BMC Genomics,8:166.
Lim LP, Lau NC, Weinstein EG, et al.2003. The microRNAs of Caenorhabditis elegans[J]. Genes Dev,17:991-1008.
Liu FJ, Wen T and Liu L.2012. MicroRNAs as a novel cellular senescence regulator[J]. Ageing Research Reviews,11:41-50.
Liu JD, Valencia-Sanchez MA, Hannon GJ, et al.2005. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies[J]. Nature Cell Biology,7:719-U118.
Liu ZL, Wang H, Liu J, et al.2013. MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo-or radioresistance in non-small cell lung cancer cells by targeting PTEN[J]. Mol Cell Biochem,372:35-45.
Lize M, Herr C, Klimke A, et al.2010a. MicroRNA-449a levels increase by several orders of magnitude during mucociliary differentiation of airway epithelia[J]. Cell Cycle,9:4579-4583.
Lize M, Pilarski S and Dobbelstein M.2010b. E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis[J]. Cell Death Differ,17:452-458.
Loffler D, Brocke-Heidrich K, Pfeifer G, et al.2007. Interleukin-6-dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer[J]. Blood,110:1330-1333.
Lowe SW.1999. Hot papers -Cancer- Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a by M. Serrano, A.W. Lin, M.E. McCurrach, D. Beach, S.W. Lowe-Comments[J]. Scientist,13:15-15.
Lu J, Getz G, Miska EA, et al.2005a. MicroRNA expression profiles classify human cancers[J]. Nature,435:834-838.
Lu J, Getz G, Miska EA, et al.2005b. MicroRNA expression profiles classify human cancers[J]. Nature,435:834-838.
Lu L, Katsaros D, de la Longrais IA, et al.2007. Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-Ⅱ expression and favorable prognosis[J]. Cancer Res,67:10117-10122.
Lujambio A, Calin GA, Villanueva A, et al.2008. A microRNA DNA methylation signature for human cancer metastasis [J]. Proceedings of the National Academy of Sciences of the United States of America,105:13556-13561.
Lujambio A, Ropero S, Ballestar E, et al.2007. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells[J]. Cancer Res,67:1424-1429.
Lund E and Dahlberg JE.2006. Substrate selectivity of Exportin 5 and Dicer in the biogenesis of microRNAs[J]. Cold Spring Harbor Symposia on Quantitative Biology,71:59-66.
Lund E, Guttinger S, Calado A, et al.2004. Nuclear export of microRNA precursors[J]. Science, 303:95-98.
Ma L.2010. Role of miR-10b in breast cancer metastasis[J]. Breast Cancer Research,12:210.
Maehara K, Yamakoshi K, Ohtani N, et al.2005. Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53[J]. Journal of Cell Biology,168:553-560.
Mattes J, Yang M and Foster PS.2007. Regulation of microRNA by antagomirs:a new class of pharmacological antagonists for the specific regulation of gene function?[J]. Am J Respir Cell Mol Biol,36:8-12.
McLemore MS, Childs GJ, Schlecht NF, et al.2008. miR-21 upregulation and loss of PTEN expression in head & neck squamous cell carcinoma[J]. Laboratory Investigation, 88:239a-239a.
Medina R, Zaidi SK, Liu CG, et al.2008. MicroRNAs 221 and 222 bypass quiescence and compromise cell survival[J]. Cancer Res,68:2773-2780.
Meng F, Wehlbe-Janek H, Henson R, et al.2007. Microrna-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular carcinoma[J]. Gastroenterology, 132:A730-A730.
Metzler M, Wilda M, Busch K, et al.2004. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma[J]. Genes Chromosomes & Cancer,39:167-169.
Michael MZ, SM OC, van Hoist Pellekaan NG, et al.2003. Reduced accumulation of specific microRNAs in colorectal neoplasia[J]. Molecular Cancer Research,1:882-891.
Miska EA.2007. Microrna expression profiles classify human cancers[J]. Cytometry Part B-Clinical Cytometry,72B:126-126.
Morlando M, Ballarino M, Gromak N, et al.2008. Primary microRNA transcripts are processed co-transcriptionally[J]. Nat Struct Mol Biol,15:902-909.
Moss EG, Lee RC and Ambros V.1997. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA[J]. Cell,88:637-646.
Motoyama K, Inoue H, Nakamura Y, et al.2008. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family[J]. Clin Cancer Res, 14:2334-2340.
Mu LN, Liu L, Niu RG, et al.2013. Indoor air pollution and risk of lung cancer among Chinese female non-smokers[J]. Cancer Causes & Control,24:439-450.
Murchison EP and Hannon GJ.2004. MiRNAs on the move:miRNA biogenesis and the RNAi machinery[J]. Current Opinion in Cell Biology,16:223-229.
Noguchi S, Mori T, Otsuka Y, et al.2012. Anti-oncogenic MicroRNA-203 Induces Senescence by Targeting E2F3 Protein in Human Melanoma Cells[J]. Journal of Biological Chemistry, 287:11769-11777.
Noonan EJ, Place RF, Basak S, et al.2010. miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells[J]. Oncotarget,1:349-358.
Noonan EJ, Place RF, Pookot D, et al.2009. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer[J]. Oncogene,28:1714-1724.
O'Connell RM, Taganov KD, Boldin MP, et al.2007. MicroRNA-155 is induced during the macrophage inflammatory response[J]. Proceedings of the National Academy of Sciences of the United States of America,104:1604-1609.
O'Donnell KA, Wentzel EA, Zeller KI, et al.2005. c-Myc-regulated microRNAs modulate E2F1 expression[J]. Nature,435:839-843.
Oeggerli M, Tomovska S, Schraml P, et al.2004. E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer[J]. Oncogene,23:5616-5623.
Ota A, Tagawa H, Karnan S, et al.2004. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma[J]. Cancer Res, 64:3087-3095.
Paik S, Jung HS, Lee S, et al.2012. miR-449a Regulates the Chondrogenesis of Human Mesenchymal Stem Cells Through Direct Targeting of Lymphoid Enhancer-Binding Factor-1[J]. Stem Cells and Development,21:3298-3308.
Pasquinelli AE, Reinhart BJ, Slack F, et al.2000. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA[J]. Nature,408:86-89.
Pickering MT, Stadler BM and Kowalik TF.2009. miR-17 and miR-20a temper an E2F1-induced G1 checkpoint to regulate cell cycle progression[J]. Oncogene,28:140-145.
Pierson J, Hostager B, Fan R, et al.2008. Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma[J]. Journal of Neuro-Oncology,90:1-7.
Pillai RS, Bhattacharyya SN, Artus CG, et al.2005. Inhibition of translational initiation by Let-7 microRNA in human cells[J]. Science,309:1573-1576.
Proctor RN.2001. Tobacco and the global lung cancer epidemic[J]. Nature Reviews Cancer, 1:82-86.
Przemeck GK, Heinzmann U, Beckers J, et al.2003. Node and midline defects are associated with left-right development in Deltal mutant embryos[J]. Development,130:3-13.
Rana TM.2007. Illuminating the silence:understanding the structure and function of small RNAs[J]. Nature Reviews Molecular Cell Biology,8:23-36.
Raver-Shapira N, Marciano E, Meiri E, et al.2007a. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis[J], Mol Cell,26:731-743.
Raver-Shapira N, Marciano E, Meiri E, et al.2007b. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis[J]. Mol Cell,26:731-743.
Reinhart BJ, Slack FJ, Basson M, et al.2000. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans[J]. Nature,403:901-906.
Rho JK, Choi YJ, Ryoo BY, et al.2007. p53 enhances gefitinib-induced growth inhibition and apoptosis by regulation of Fas in non-small cell lung cancer[J]. Cancer Res,67:1163-1169.
Roberts PJ, Stinchcombe TE, Der CJ, et al.2010. Personalized medicine in non-small-cell lung cancer:is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy?[J]. Journal of Clinical Oncology,28:4769-4777.
Ruvkun G and Giusto J.1989. The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch[J]. Nature,338:313-319.
Ryan BM, Robles Al and Harris CC.2010. Genetic variation in microRNA networks:the implications for cancer research (vol 10, pg 389,2010)[J]. Nature Reviews Cancer,10.
Saito Y, Liang G, Egger G, et al.2006. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells[J]. Cancer Cell,9:435-443.
Schmitt CA.2007. Cellular senescence and cancer treatment[J]. Biochimica Et Biophysica Acta-Reviews on Cancer,1775:5-20.
Schwarz DS, Hutvagner G, Du T, et al.2003. Asymmetry in the assembly of the RNAi enzyme complex[J]. Cell,115:199-208.
Sen GL and Blau HM.2005. Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies[J]. Nature Cell Biology,7:633-U628.
Shay JW and Roninson IB.2004. Hallmarks of senescence in carcinogenesis and cancer therapy[J]. Oncogene,23:2919-2933.
Sherr CJ.1996. Cancer cell cycles[J]. Science,274:1672-1677.
Shimizu E, Coxon A, Otterson GA, et al.1994. RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma[J]. Oncogene,9:2441-2448.
Si ML, Zhu S, Wu H, et al.2007. miR-21-mediated tumor growth[J]. Oncogene,26:2799-2803.
Siegel R, Naishadham D and Jemal A.2012. Cancer Statistics,2012[J]. Ca-a Cancer Journal for Clinicians,62:10-29.
Slack FJ, Basson M, Liu Z, et al.2000. The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor[J]. Mol Cell,5:659-669.
Sloan CD, Andrew AS, Gruber JF, et al.2012. Indoor and outdoor air pollution and lung cancer in New Hampshire and Vermont[J]. Toxicological and Environmental Chemistry,94:605-615.
Srikantan S, Gorospe M and Abdelmohsen K.2011. Senescence-associated microRNAs linked to tumorigenesis[J]. Cell Cycle,10:3211-3212.
Stancakova A, Pihlajamaki J, Kuusisto J, et al.2008. Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance[J]. Journal of Clinical Endocrinology & Metabolism,93:1924-1930.
Sun YH, Fang R, Li CG, et al.2010. Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro[J]. Biochem Biophys Res Commun,396:501-507.
Sylvestre Y, De Guire V, Querido E, et al.2007. An E2F/miR-20a autoregulatory feedback loop[J]. Journal of Biological Chemistry,282:2135-2143.
Takagi T, Iio A, Nakagawa Y, et al.2009. Decreased Expression of MicroRNA-143 and-145 in Human Gastric Cancers[J]. Oncology,77:12-21.
Takamizawa J, Konishi H, Yanagisawa K, et al.2004a. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival[J]. Cancer Research,64:3753-3756.
Takamizawa J, Konishi H, Yanagisawa K, et al.2004b. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival[J]. Cancer Res,64:3753-3756.
Tarasov V, Jung P, Verdoodt B, et al.2007. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing:miR-34a is a p53 target that induces apoptosis and G1-arrest[J]. Cell Cycle,6:1586-1593.
Tazawa H, Tsuchiya N, Izumiya M, et al.2007a. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells[J]. Proceedings of the National Academy of Sciences of the United States of America, 104:15472-15477.
Tazawa H, Tsuchiya N, Izumiya M, et al.2007b. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells[J]. Proc Natl Acad Sci U S A,104:15472-15477.
Thun MJ, Hannan LM, Adams-Campbell LL, et al.2008. Lung Cancer Occurrence in Never-Smokers:An Analysis of 13 Cohorts and 22 Cancer Registry Studies[J]. Plos Medicine, 5:1357-1371.
van't Veer LJ, Dai H, van de Vijver MJ, et al.2002. Gene expression profiling predicts clinical outcome of breast cancer[J]. Nature,415:530-536.
Vogelstein B and Kinzler KW.2004. Cancer genes and the pathways they control[J].Nature Medicine,10:789-799.
Volinia S, Calin GA, Liu CG, et al.2006a. A microRNA expression signature of human solid tumors defines cancer gene targets[J]. Proceedings of the National Academy of Sciences of the United States of America,103:2257-2261.
Volinia S, Calin GA, Liu CG, et al.2006b. A microRNA expression signature of human solid tumors defines cancer gene targets[J]. Proc Natl Acad Sci U S A,103:2257-2261.
Voorhoeve PM, le Sage C, Schrier M, et al.2006. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors[J]. Cell,124:1169-1181.
Wang G, Mao W and Zheng S.2008. MicroRNA-183 regulates Ezrin expression in lung cancer cells[J]. FEBS Lett,582:3663-3668.
Wang Z and Burke PA.2013. The role of microRNAs in hepatocyte nuclear factor-4alpha expression and transactivation[J]. Biochim Biophys Acta,1829:436-442.
Watt AJ, Garrison WD and Duncan SA.2003. HNF4:a central regulator of hepatocyte differentiation and function[J]. Hepatology,37:1249-1253.
Wei J, Gao W, Zhu CJ, et al.2011. Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer[J]. Chin J Cancer,30:407-414.
Weiler J, Hunziker J and Hall J.2006. Anti-miRNA oligonucleotides (AMOs):ammunition to target miRNAs implicated in human disease?[J]. Gene Ther,13:496-502.
Welch C, Chen Y and Stallings RL.2007. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells[J]. Oncogene,26:5017-5022.
Wendler A, Keller D, Albrecht C, et al.2011. Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells[J]. Oncol Rep,25:273-279.
Wightman B, Burglin TR, Gatto J, et al.1991. Negative regulatory sequences in the lin-14 3'-untranslated region are necessary to generate a temporal switch during Caenorhabditis elegans development[J]. Genes Dev,5:1813-1824.
Wightman B, Ha I and Ruvkun G.1993. Posttranscriptional Regulation of the Heterochronic Gene Lin-14 by Lin-4 Mediates Temporal Pattern-Formation in C-Elegans[J]. Cell,75:855-862.
Wolterbeek APM, Schoevers EJ, Rutten AAJJL, et al.1995. A Critical-Appraisal of Intratracheal Instillation of Benzo[a]Pyrene to Syrian Golden-Hamsters as a Model in Respiratory-Tract Carcinogenesis[J]. Cancer Lett,89:107-116.
Wu L and Belasco JG.2008. Let me count the ways:Mechanisms of gene regulation by miRNAs and siRNAs[J]. Mol Cell,29:1-7.
Wu LG, Fan JH and Belasco JG.2006. MicroRNAs direct rapid deadenylation of mRNA[J]. Proceedings of the National Academy of Sciences of the United States of America, 103:4034-4039.
Wu LZ, Timmers C, Maiti B, et al.2001. The E2F1-3 transcription factors are essential for cellular proliferation[J]. Nature,414:457-462.
Wu Q, Jin HF, Yang ZP, et al.2010. MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2[J]. Biochem Biophys Res Commun,392:340-345.
Xi Y, Formentini A, Chien M, et al.2006. Prognostic Values of microRNAs in Colorectal Cancer[J]. Biomark Insights,2:113-121.
Xiao BX, Guo JM, Miao Y, et al.2009. Detection of miR-106a in gastric carcinoma and its clinical significance[J]. Clinica Chimica Acta,400:97-102.
Xie Y, Todd NW, Liu Z, et al.2010. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer[J]. Lung Cancer,67:170-176.
Yanaihara N, Caplen N, Bowman E, et al.2006a. Unique MicroRNA molecular profiles in lung cancer diagnosis and prognosis[J]. Toxicologic Pathology,34:1017-1018.
Yanaihara N, Caplen N, Bowman E, et al.2006b. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis[J]. Cancer Cell,9:189-198.
Yang XJ, Feng M, Jiang X, et al.2009. miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A[J]. Genes Dev,23:2388-2393.
Yang Y, Li XF, Yang Q, et al.2010. The role of microRNA in human lung squamous cell carcinoma[J]. Cancer Genetics and Cytogenetics,200:127-133.
Yu F, Yao H, Zhu P, et al.2007. let-7 regulates self renewal and tumorigenicity of breast cancer cells[J].Cell,131:1109-1123.
Yu SL, Chen HY, Chang GC, et al.2008a. MicroRNA signature predicts survival and relapse in lung cancer[J]. Cancer Cell,13:48-57.
Yu SL, Chen HY, Chang GC, et al.2008b. MicroRNA signature predicts survival and relapse in lung cancer[J]. Cancer Cell,13:48-57.
Zhang BH, Pan XP, Cobb GP, et al.2007. microRNAs as oncogenes and tumor suppressors[J]. Developmental Biology,302:1-12.
Zhang JG, Wang JJ, Zhao F, et al.2010. MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC)[J]. Clinica Chimica Acta,411:846-852.
Zhao Y, Wang SX, Aunan K, et al.2006. Air pollution and lung cancer risks in China-a meta-analysis[J]. Science of the Total Environment,366:500-513.
Zhao YC, Deng CS, Wang JR, et al.2011. Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer[J]. Breast Cancer Res Treat,127:69-80.
Zhu S, Si ML, Wu H, et al.2007. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1)[J].J Biol Chem,282:14328-14336.
Ambros V.1989. A Hierarchy of Regulatory Genes Controls a Larva-to-Adult Developmental Switch in C-Elegans[J]. Cell,57:49-57.
Ambros V, Bartel B, Bartel DP, et al.2003. A uniform system for microRNA annotation[J]. RNA, 9:277-279.
Asangani IA, Rasheed SA, Nikolova DA, et al.2008. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer[J].Oncogene,27:2128-2136.
Bandi N and Vassella E.2011. miR-34a and miR-15a/16 are co-regulated in non-small cell lung cancer and control cell cycle progression in a synergistic and Rb-dependent manner[J]. Mol Cancer,10.
Bandres E, Bitarte N, Arias F, et al.2009. microRNA-451 Regulates Macrophage Migration Inhibitory Factor Production and Proliferation of Gastrointestinal Cancer Cells[J]. Clinical Cancer Research,15:2281-2290.
Bartel DP.2004. MicroRNAs:Genomics, biogenesis, mechanism, and function[J]. Cell, 116:281-297.
Bartel DP.2007. MicroRNAs:Genomics, biogenesis, mechanism, and function (Reprinted from Cell,vol 116, pg 281-297,2004)[J]. Cell,131:11-29.
Bartel DP.2009. MicroRNAs:Target Recognition and Regulatory Functions[J]. Cell, 136:215-233.
Behm-Ansmant I, Rehwinkel J, Doerks T, et al.2006. mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes[J]. Genes Dev,20:1885-1898.
Bernstein E, Caudy AA, Hammond SM, et al.2001. Role for a bidentate ribonuclease in the initiation step of RNA interference[J]. Nature,409:363-366.
Boffetta P and Nyberg F.2003. Contribution of environmental factors to cancer risk[J]. British Medical Bulletin,68:71-94.
Bohnsack MT, Czaplinski K and Gorlich D.2004. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs[J]. RNA,10:185-191.
Bommer GT, Gerin I, Feng Y, et al.2007. p53-mediated activation of miRNA34 candidate tumor-suppressor genes[J]. Curr Biol,17:1298-1307.
Borchert GM, Lanier W and Davidson BL.2006. RNA polymerase III transcribes human microRNAs[J]. Nature Structural & Molecular Biology,13:1097-1101.
Bou Kheir T, Futoma-Kazmierczak E, Jacobsen A, et al.2011. miR-449 inhibits cell proliferation and is down-regulated in gastric cancer[J]. Molecular Cancer,10:29.
Brooker R, Hozumi K and Lewis J.2006. Notch ligands with contrasting functions:Jagged1 and Deltal in the mouse inner ear[J]. Development,133:1277-1286.
Calin GA.2006. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia (vol 353, pg 1793,2005)[J]. New England Journal of Medicine, 355:533-533.
Calin GA and Croce CM.2006. MicroRNA signatures in human cancers[J]. Nature Reviews Cancer,6:857-866.
Calin GA, Dumitru CD, Shimizu M, et al.2002. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia[J]. Proceedings of the National Academy of Sciences of the United States of America, 99:15524-15529.
Calin GA, Ferracin M, Cimmino A, et al.2005. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia[J]. New England Journal of Medicine, 353:1793-1801.
Calin GA, Sevignani C, Dan Dumitru C, et al.2004. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers[J]. Proceedings of the National Academy of Sciences of the United States of America,101:2999-3004.
Campisi J.2005. Senescent cells, tumor suppression, and organismal aging:Good citizens, bad neighbors[J]. Cell,120:513-522.
Capuano M, Iaffaldano L, Tinto N, et al.2011. MicroRNA-449a overexpression, reduced NOTCH1 signals and scarce goblet cells characterize the small intestine of celiac patients[J]. PLoS One,6:e29094.
Carmell MA and Hannon GJ.2004. RNase III enzymes and the initiation of gene silencing[J]. Nat Struct Mol Biol,11:214-218.
Carthew RW and Sontheimer EJ.2009. Origins and Mechanisms of miRNAs and siRNAs[J]. Cell, 136:642-655.
Chan JA, Krichevsky AM and Kosik KS.2005. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells[J]. Cancer Res,65:6029-6033.
Chang TC, Wentzel EA, Kent OA, et al.2007a. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis[J]. Mol Cell,26:745-752.
Chang TC, Wentzel EA, Kent OA, et al.2007b. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis[J]. Mol Cell,26:745-752.
Chen CZ, Li L, Lodish HF, et al.2004. MicroRNAs modulate hematopoietic lineage differentiation[J]. Science,303:83-86.
Chen H, Lin YW, Mao YQ, et al.2012. MicroRNA-449a acts as a tumor suppressor in human bladder cancer through the regulation of pocket proteins[J]. Cancer Letters,320:40-47.
Chen WH, Bochmann F and Sun Y.2007. Effects of work related confounders on the association between silica exposure and lung cancer:a nested case-control study among Chinese miners and pottery workers[J]. International Archives of Occupational and Environmental Health, 80:320-326.
Chen YC, Davidson B, Cheng CC, et al.2005. Identification and characterization of membralin, a novel tumor-associated gene, in ovarian carcinoma[J]. Biochim Biophys Acta,1730:96-102.
Chendrimada TP, Finn KJ, Ji XJ, et al.2007. MicroRNA silencing through RISC recruitment of eIF6[J]. Nature,447:823-U821.
Cheng YW, Chiou HL, Sheu GT, et al.2001. The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women[J]. Cancer Res, 61:2799-2803.
Chiu HF, Cheng MH, Tsai SS, et al.2006. Outdoor air pollution and female lung cancer in Taiwan[J]. Inhalation Toxicology,18:1025-1031.
Choi N, Baumann M, Flentjie M, et al.2001. Predictive factors in radiotherapy for non-small cell lung cancer:present status[J]. Lung Cancer,31:43-56.
Ciafre SA, Galardi S, Mangiola A, et al.2005. Extensive modulation of a set of microRNAs in primary glioblastoma[J]. Biochem Biophys Res Commun,334:1351-1358.
Cocco P, Rice CH, Chen JQ, et al.2001. Lung cancer risk, silica exposure, and silicosis in Chinese mines and pottery factories:The modifying role of other workplace lung carcinogens[J]. Am J Ind Med,40:674-682.
Coieman WB and Tsongalis GJ.2006. Molecular mechanisms of human carcinogenesis[J]. EXS:321-349.
Collado M, Blasco MA and Serrano M.2007. Cellular senescence in cancer and aging[J]. Cell, 130:223-233.
Cooper CS, Nicholson AG,Foster C, et al.2006. Nuclear overexpression of the E2F3 transcription factor in human lung cancer[J]. Lung Cancer,54:155-162.
Corsten MF, Miranda R, Kasmieh R, et al.2007. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas[J]. Cancer Res,67:8994-9000.
Costa RH, Kalinichenko VV, Holterman AX, et al.2003. Transcription factors in liver development, differentiation, and regeneration[J]. Hepatology,38:1331-1347.
Cullen BR.2004. Transcription and processing of human microRNA precursors[J]. Mol Cell, 16:861-865.
Donnem T, Eklo K, Berg T, et al.2011. Prognostic Impact of MiR-155 in Non-Small Cell Lung Cancer Evaluated by in Situ Hybridization[J]. Journal of Translational Medicine,9.
Duan RH, Pak CH and Jin P.2007. Single nucleotide polymorphism associated with mature miR-125 a alters the processing o f pri-miRNA [J]. Human Molecular Genetics,16:1124-1131.
Dutta KK, Zhong Y, Liu YT, et al.2007. Association of microRNA-34a overexpression with proliferation is cell type-dependent[J]. Cancer Science,98:1845-1852.
Eberharter A and Becker PB.2002. Histone acetylation:a switch between repressive and permissive chromatin-Second in review series on chromatin dynamics[J]. Embo Reports, 3:224-229.
Eis PS, Tam W, Sun LP, et al.2005. Accumulation of miR-155 and BIC RNA in human B cell lymphomas[J]. Proceedings of the National Academy of Sciences of the United States of America,102:3627-3632.
Erren TC, Morfeld P, Glende CB, et al.2007. Silica and lung cancer[J]. Epidemiology, 18:521-521.
Farazi TA, Juranek SA and Tuschl T.2008. The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members[J]. Development,135:1201-1214.
Feng SP, Cong SJ, Zhang X, et al.2011. MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells[J]. Nucleic Acids Res, 39:6669-6678.
Field RW, Krewski D, Lubin JH, et al.2006. An overview of the North American residential radon and lung cancer case-control studies[J]. J Toxicol Environ Health A,69:599-631.
Filipowicz W, Bhattacharyya SN and Sonenberg N.2008. Mechanisms of post-transcriptional regulation by microRNAs:are the answers in sight?[J]. Nature Reviews Genetics,9:102-114.
Fire A, Xu S, Montgomery MK, et al.1998. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans[J]. Nature,391:806-811.
Foster CS, Falconer A, Dodson AR, et al.2004. Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome[J]. Oncogene,23:5871-5879.
Fraga MF and Esteller M.2005. Towards the human cancer epigenome -A first draft of histone modifications[J]. Cell Cycle,4:1377-1381.
Friedman RC, Farh KKH, Burge CB, et al.2009. Most mammalian mRNAs are conserved targets of microRNAs[J]. Genome Research,19:92-105.
Frisch M, Biggar RJ, Engels EA, et al.2001. Association of cancer with AIDS-related immunosuppression in adults[J]. Jama-Journal of the American Medical Association, 285:1736-1745.
Galardi S, Mercatelli N, Giorda E, et al.2007. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1[J]. J Biol Chem,282:23716-23724.
Gallardo E, Navarro A, Vinolas N, et al.2009. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer[J]. Carcinogenesis,30:1903-1909.
Giraldez AJ, Mishima Y, Rihel J, et al.2006. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs[J]. Science,312:75-79.
Granville CA and Dennis PA.2005. An overview of lung cancer genomics and proteomics[J]. Am J Respir Cell Mol Biol,32:169-176.
Gregory RI, Yan KP, Amuthan G, et al.2004. The Microprocessor complex mediates the genesis of microRNAs[J]. Nature,432:235-240.
Grun D, Wang YL, Langenberger D, et al.2005. MicroRNA target predictions across seven Drosophila species and comparison to mammalian targets[J]. Plos Computational Biology, 1:51-66.
Guarnieri DJ and Dileone RJ.2008. MicroRNAs:A new class of gene regulators[J]. Annals of Medicine,40:197-208.
Gwizdek C, Ossareh-Nazari B, Brownawell AM, et al.2003. Exportin-5 mediates nuclear export of minihelix-containing RNAs[J]. J Biol Chem,278:5505-5508.
Han JJ, Lee Y, Yeom KH, et al.2004. The Drosha-DGCR8 complex in primary microRNA processing[J]. Genes Dev,18:3016-3027.
Harbour JW, Lai SL, Whangpeng J, et al.1988. Abnormalities in Structure and Expression of the Human Retinoblastoma Gene in Sclc[J]. Science,241:353-357.
Hayashita Y, Osada H, Tatematsu Y, et al.2005. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation[J]. Cancer Res, 65:9628-9632.
He H, Jazdzewski K, Li W, et al.2005a. The role of microRNA genes in papillary thyroid carcinoma[J]. Proc Natl Acad Sci U S A,102:19075-19080.
He L, He X, Lim LP, et al.2007a. A microRNA component of the p53 tumour suppressor network[J]. Nature,447:1130-1134.
He L, He XY, Lim LP, et al.2007b. A microRNA component of the p53 tumour suppressor network[J]. Nature,447:1130-U1116.
He L, Thomson JM, Hemann MT, et al.2005b. A microRNA polycistron as a potential human oncogene[J]. Nature,435:828-833.
Hennekens CH, Buring JE, Manson JE, et al.1996. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease[J]. N Engl J Med,334:1145-1149.
Hoesel B, Bhujabal Z, Przemeck GK, et al.2010. Combination of in silico and in situ hybridisation approaches to identify potential Dill associated miRNAs during mouse embryogenesis[J]. Gene Expr Patterns,10:265-273.
Hornsby PJ.2007. Senescence as an anticancer mechanism[J]. Journal of Clinical Oncology, 25:1852-1857.
Hutvagner G and Simard MJ.2008. Argonaute proteins:key players in RNA silencing[J]. Nature Reviews Molecular Cell Biology,9:22-32.
Iorio MV, Ferracin M, Liu CG, et al.2005. MicroRNA gene expression deregulation in human breast cancer[J]. Cancer Res,65:7065-7070.
Ivan M.2008. The ongoing microRNA revolution and its impact in biology and medicine FOREWORD[J]. Journal of Cellular and Molecular Medicine,12:1425-1425.
Ivanovska I, Ball AS, Diaz RL, et al.2008. MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression[J]. Molecular and Cellular Biology, 28:2167-2174.
Jassem E and Jassem J.1996. [Mutation of gene p53 in lung cancer][J]. Pneumonol Alergol Pol, 64:5-10.
Jemal A, Bray F, Center MM, et al.2011. Global cancer stati sties [J]. CA Cancer J Clin,61:69-90.
Jeong HC, Kim EK, Lee JH, et al.2011. Aberrant expression of let-7a miRNA in the blood of non-small cell lung cancer patients[J]. Molecular Medicine Reports,4:383-387.
Johnson SM, Grosshans H, Shingara J, et al.2005. RAS is regulated by the let-7 MicroRNA family[J]. Cell,120:635-647.
Jones PA and Baylin SB.2002. The fundamental role of epigenetic events in cancer[J]. Nature Reviews Genetics,3:415-428.
Joseph B, Lewensohn R and Zhivotovsky B.2000. Role of apoptosis in the response of lung carcinomas to anti-cancer treatment[J]. Ann N Y Acad Sci,926:204-216.
Kaghad M, Bonnet H, Yang A, et al.1997. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers[J]. Cell,90:809-819.
Karube Y, Tanaka H, Osada H, et al.2005. Reduced expression of Dicer associated with poor prognosis in lung cancer patients[J]. Cancer Science,96:111-115.
Khvorova A, Reynolds A and Jayasena SD.2003. Functional siRNAs and miRNAs exhibit strand bias(vol 115, pg 209,2003)[J]. Cell,115:505-505.
Kiernan AE, Cordes R, Kopan R, et al.2005. The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear[J]. Development, 132:4353-4362.
Kim VN.2004. MicroRNA precursors in motion:exportin-5 mediates their nuclear export[J]. Trends in Cell Biology,14:156-159.
Kim VN, Han J and Siomi MC.2009. Biogenesis of small RNAs in animals[J]. Nat Rev Mol Cell Biol,10:126-139.
Kim YK and Kim VN.2007. Processing of intronic microRNAs[J]. Embo Journal,26:775-783.
Kiriakidou M, Tan GS, Lamprinaki S, et al.2007. An mRNA m7G cap binding-like motif within human Ago2 represses translation[J]. Cell,129:1141-1151.
Kluiver J, Poppema S, de Jong D, et al.2005. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas[J]. Journal of Pathology, 207:243-249.
Kluiver J, van den Berg A, de Jong D, et al.2007. Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma[J]. Oncogene,26:3769-3776.
Kong W, Yang H, He L, et al.2008. MicroRNA-155 Is Regulated by the Transforming Growth Factor beta/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA[J]. Molecular and Cellular Biology,28:6773-6784.
Kovesdi I, Reichel R and Nevins JR.1986. Identification of a Cellular Transcription Factor Involved in Ela Transactivation[J]. Cell,45:219-228.
Krutzfeldt J, Rajewsky N, Braich R, et al.2005. Silencing of microRNAs in vivo with 'antagomirs'[J]. Nature,438:685-689.
Lachet B.2006. Indoor radon and lung cancer[J]. Epidemiology,17:121; author reply 121-122.
Lagos-Quintana M, Rauhut R, Lendeckel W, et al.2001. Identification of novel genes coding for small expressed RNAs[J]. Science,294:853-858.
Lam WK, White NW and Chan-Yeung MM.2004. Lung cancer epidemiology and risk factors in Asia and Africa[J]. International Journal of Tuberculosis and Lung Disease,8:1045-1057.
Lau NC, Lim LP, Weinstein EG, et al.2001. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans[J]. Science,294:858-862.
Lawrie CH, Soneji S, Marafioti T, et al.2007. MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma[J]. International Journal of Cancer,121:1156-1161.
Lee RC and Ambros V.2001. An extensive class of small RNAs in Caenorhabditis elegans[J]. Science,294:862-864.
Lee RC, Feinbaum RL and Ambros V.1993. The C-Elegans Heterochronic Gene Lin-4 Encodes Small Rnas with Antisense Complementarity to Lin-14[J]. Cell,75:843-854.
Lee Y, Ahn C, Han JJ, et al.2003. The nuclear RNase Ⅲ Drosha initiates microRNA processing[J]. Nature,425:415-419.
Lee Y, Jeon K, Lee JT, et al.2002. MicroRNA maturation:stepwise processing and subcellular localization[J]. EMBO J,21:4663-4670.
Lee Y, Kim M, Han JJ, et al.2004. MicroRNA genes are transcribed by RNA polymerase Ⅱ[J]. Embo Journal,23:4051-4060.
Lee YS and Dutta A.2007. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene[J]. Genes Dev,21:1025-1030.
Lehmann U, Hasemeier B, Christgen M, et al.2008. Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer[J]. Journal of Pathology,214:17-24.
Leone G, DeGregori J, Yan Z, et al.1998. E2F3 activity is regulated during the cell cycle and is required for the induction of S phase[J]. Genes & Development,12:2120-2130.
Leone G, Sears R, Huang E, et al.2001. Myc requires distinct E2F activities to induce S phase and apoptosis[J]. Molecular Cell,8:105-113.
Lewis BP, Shih IH, Jones-Rhoades MW, et al.2003. Prediction of mammalian microRNA targets[J]. Cell,115:787-798.
Li AL and Mao L.2007. Evolution of plant microRNA gene families[J]. Cell Research, 17:212-218.
Liang Y.2008. An expression meta-analysis of predicted microRNA targets identifies a diagnostic signature for lung cancer[J]. BMC Med Genomics,1:61.
Liang Y, Ridzon D, Wong L, et al.2007. Characterization of microRNA expression profiles in normal human tissues[J]. BMC Genomics,8:166.
Lim LP, Lau NC, Weinstein EG, et al.2003. The microRNAs of Caenorhabditis elegans[J]. Genes Dev,17:991-1008.
Liu FJ, Wen T and Liu L.2012. MicroRNAs as a novel cellular senescence regulator[J]. Ageing Research Reviews,11:41-50.
Liu JD, Valencia-Sanchez MA, Hannon GJ, et al.2005. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies[J]. Nature Cell Biology,7:719-U118.
Liu ZL, Wang H, Liu J, et al.2013. MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo-or radioresistance in non-small cell lung cancer cells by targeting PTEN[J]. Mol Cell Biochem,372:35-45.
Lize M, Herr C, Klimke A, et al.2010a. MicroRNA-449a levels increase by several orders of magnitude during mucociliary differentiation of airway epithelia[J]. Cell Cycle,9:4579-4583.
Lize M, Pilarski S and Dobbelstein M.2010b. E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis[J]. Cell Death Differ,17:452-458.
Loffler D, Brocke-Heidrich K, Pfeifer G, et al.2007. Interleukin-6-dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer[J]. Blood,110:1330-1333.
Lowe SW.1999. Hot papers -Cancer- Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a by M. Serrano, A.W. Lin, M.E. McCurrach, D. Beach, S.W. Lowe-Comments[J]. Scientist,13:15-15.
Lu J, Getz G, Miska EA, et al.2005a. MicroRNA expression profiles classify human cancers[J]. Nature,435:834-838.
Lu J, Getz G, Miska EA, et al.2005b. MicroRNA expression profiles classify human cancers[J]. Nature,435:834-838.
Lu L, Katsaros D, de la Longrais IA, et al.2007. Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-Ⅱ expression and favorable prognosis[J]. Cancer Res,67:10117-10122.
Lujambio A, Calin GA, Villanueva A, et al.2008. A microRNA DNA methylation signature for human cancer metastasis [J]. Proceedings of the National Academy of Sciences of the United States of America,105:13556-13561.
Lujambio A, Ropero S, Ballestar E, et al.2007. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells[J]. Cancer Res,67:1424-1429.
Lund E and Dahlberg JE.2006. Substrate selectivity of Exportin 5 and Dicer in the biogenesis of microRNAs[J]. Cold Spring Harbor Symposia on Quantitative Biology,71:59-66.
Lund E, Guttinger S, Calado A, et al.2004. Nuclear export of microRNA precursors[J]. Science, 303:95-98.
Ma L.2010. Role of miR-10b in breast cancer metastasis[J]. Breast Cancer Research,12:210.
Maehara K, Yamakoshi K, Ohtani N, et al.2005. Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53[J]. Journal of Cell Biology,168:553-560.
Mattes J, Yang M and Foster PS.2007. Regulation of microRNA by antagomirs:a new class of pharmacological antagonists for the specific regulation of gene function?[J]. Am J Respir Cell Mol Biol,36:8-12.
McLemore MS, Childs GJ, Schlecht NF, et al.2008. miR-21 upregulation and loss of PTEN expression in head & neck squamous cell carcinoma[J]. Laboratory Investigation, 88:239a-239a.
Medina R, Zaidi SK, Liu CG, et al.2008. MicroRNAs 221 and 222 bypass quiescence and compromise cell survival[J]. Cancer Res,68:2773-2780.
Meng F, Wehlbe-Janek H, Henson R, et al.2007. Microrna-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular carcinoma[J]. Gastroenterology, 132:A730-A730.
Metzler M, Wilda M, Busch K, et al.2004. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma[J]. Genes Chromosomes & Cancer,39:167-169.
Michael MZ, SM OC, van Hoist Pellekaan NG, et al.2003. Reduced accumulation of specific microRNAs in colorectal neoplasia[J]. Molecular Cancer Research,1:882-891.
Miska EA.2007. Microrna expression profiles classify human cancers[J]. Cytometry Part B-Clinical Cytometry,72B:126-126.
Morlando M, Ballarino M, Gromak N, et al.2008. Primary microRNA transcripts are processed co-transcriptionally[J]. Nat Struct Mol Biol,15:902-909.
Moss EG, Lee RC and Ambros V.1997. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA[J]. Cell,88:637-646.
Motoyama K, Inoue H, Nakamura Y, et al.2008. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family[J]. Clin Cancer Res, 14:2334-2340.
Mu LN, Liu L, Niu RG, et al.2013. Indoor air pollution and risk of lung cancer among Chinese female non-smokers[J]. Cancer Causes & Control,24:439-450.
Murchison EP and Hannon GJ.2004. MiRNAs on the move:miRNA biogenesis and the RNAi machinery[J]. Current Opinion in Cell Biology,16:223-229.
Noguchi S, Mori T, Otsuka Y, et al.2012. Anti-oncogenic MicroRNA-203 Induces Senescence by Targeting E2F3 Protein in Human Melanoma Cells[J]. Journal of Biological Chemistry, 287:11769-11777.
Noonan EJ, Place RF, Basak S, et al.2010. miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells[J]. Oncotarget,1:349-358.
Noonan EJ, Place RF, Pookot D, et al.2009. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer[J]. Oncogene,28:1714-1724.
O'Connell RM, Taganov KD, Boldin MP, et al.2007. MicroRNA-155 is induced during the macrophage inflammatory response[J]. Proceedings of the National Academy of Sciences of the United States of America,104:1604-1609.
O'Donnell KA, Wentzel EA, Zeller KI, et al.2005. c-Myc-regulated microRNAs modulate E2F1 expression[J]. Nature,435:839-843.
Oeggerli M, Tomovska S, Schraml P, et al.2004. E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer[J]. Oncogene,23:5616-5623.
Ota A, Tagawa H, Karnan S, et al.2004. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma[J]. Cancer Res, 64:3087-3095.
Paik S, Jung HS, Lee S, et al.2012. miR-449a Regulates the Chondrogenesis of Human Mesenchymal Stem Cells Through Direct Targeting of Lymphoid Enhancer-Binding Factor-1[J]. Stem Cells and Development,21:3298-3308.
Pasquinelli AE, Reinhart BJ, Slack F, et al.2000. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA[J]. Nature,408:86-89.
Pickering MT, Stadler BM and Kowalik TF.2009. miR-17 and miR-20a temper an E2F1-induced G1 checkpoint to regulate cell cycle progression[J]. Oncogene,28:140-145.
Pierson J, Hostager B, Fan R, et al.2008. Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma[J]. Journal of Neuro-Oncology,90:1-7.
Pillai RS, Bhattacharyya SN, Artus CG, et al.2005. Inhibition of translational initiation by Let-7 microRNA in human cells[J]. Science,309:1573-1576.
Proctor RN.2001. Tobacco and the global lung cancer epidemic[J]. Nature Reviews Cancer, 1:82-86.
Przemeck GK, Heinzmann U, Beckers J, et al.2003. Node and midline defects are associated with left-right development in Deltal mutant embryos[J]. Development,130:3-13.
Rana TM.2007. Illuminating the silence:understanding the structure and function of small RNAs[J]. Nature Reviews Molecular Cell Biology,8:23-36.
Raver-Shapira N, Marciano E, Meiri E, et al.2007a. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis[J], Mol Cell,26:731-743.
Raver-Shapira N, Marciano E, Meiri E, et al.2007b. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis[J]. Mol Cell,26:731-743.
Reinhart BJ, Slack FJ, Basson M, et al.2000. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans[J]. Nature,403:901-906.
Rho JK, Choi YJ, Ryoo BY, et al.2007. p53 enhances gefitinib-induced growth inhibition and apoptosis by regulation of Fas in non-small cell lung cancer[J]. Cancer Res,67:1163-1169.
Roberts PJ, Stinchcombe TE, Der CJ, et al.2010. Personalized medicine in non-small-cell lung cancer:is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy?[J]. Journal of Clinical Oncology,28:4769-4777.
Ruvkun G and Giusto J.1989. The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch[J]. Nature,338:313-319.
Ryan BM, Robles Al and Harris CC.2010. Genetic variation in microRNA networks:the implications for cancer research (vol 10, pg 389,2010)[J]. Nature Reviews Cancer,10.
Saito Y, Liang G, Egger G, et al.2006. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells[J]. Cancer Cell,9:435-443.
Schmitt CA.2007. Cellular senescence and cancer treatment[J]. Biochimica Et Biophysica Acta-Reviews on Cancer,1775:5-20.
Schwarz DS, Hutvagner G, Du T, et al.2003. Asymmetry in the assembly of the RNAi enzyme complex[J]. Cell,115:199-208.
Sen GL and Blau HM.2005. Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies[J]. Nature Cell Biology,7:633-U628.
Shay JW and Roninson IB.2004. Hallmarks of senescence in carcinogenesis and cancer therapy[J]. Oncogene,23:2919-2933.
Sherr CJ.1996. Cancer cell cycles[J]. Science,274:1672-1677.
Shimizu E, Coxon A, Otterson GA, et al.1994. RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma[J]. Oncogene,9:2441-2448.
Si ML, Zhu S, Wu H, et al.2007. miR-21-mediated tumor growth[J]. Oncogene,26:2799-2803.
Siegel R, Naishadham D and Jemal A.2012. Cancer Statistics,2012[J]. Ca-a Cancer Journal for Clinicians,62:10-29.
Slack FJ, Basson M, Liu Z, et al.2000. The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor[J]. Mol Cell,5:659-669.
Sloan CD, Andrew AS, Gruber JF, et al.2012. Indoor and outdoor air pollution and lung cancer in New Hampshire and Vermont[J]. Toxicological and Environmental Chemistry,94:605-615.
Srikantan S, Gorospe M and Abdelmohsen K.2011. Senescence-associated microRNAs linked to tumorigenesis[J]. Cell Cycle,10:3211-3212.
Stancakova A, Pihlajamaki J, Kuusisto J, et al.2008. Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance[J]. Journal of Clinical Endocrinology & Metabolism,93:1924-1930.
Sun YH, Fang R, Li CG, et al.2010. Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro[J]. Biochem Biophys Res Commun,396:501-507.
Sylvestre Y, De Guire V, Querido E, et al.2007. An E2F/miR-20a autoregulatory feedback loop[J]. Journal of Biological Chemistry,282:2135-2143.
Takagi T, Iio A, Nakagawa Y, et al.2009. Decreased Expression of MicroRNA-143 and-145 in Human Gastric Cancers[J]. Oncology,77:12-21.
Takamizawa J, Konishi H, Yanagisawa K, et al.2004a. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival[J]. Cancer Research,64:3753-3756.
Takamizawa J, Konishi H, Yanagisawa K, et al.2004b. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival[J]. Cancer Res,64:3753-3756.
Tarasov V, Jung P, Verdoodt B, et al.2007. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing:miR-34a is a p53 target that induces apoptosis and G1-arrest[J]. Cell Cycle,6:1586-1593.
Tazawa H, Tsuchiya N, Izumiya M, et al.2007a. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells[J]. Proceedings of the National Academy of Sciences of the United States of America, 104:15472-15477.
Tazawa H, Tsuchiya N, Izumiya M, et al.2007b. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells[J]. Proc Natl Acad Sci U S A,104:15472-15477.
Thun MJ, Hannan LM, Adams-Campbell LL, et al.2008. Lung Cancer Occurrence in Never-Smokers:An Analysis of 13 Cohorts and 22 Cancer Registry Studies[J]. Plos Medicine, 5:1357-1371.
van't Veer LJ, Dai H, van de Vijver MJ, et al.2002. Gene expression profiling predicts clinical outcome of breast cancer[J]. Nature,415:530-536.
Vogelstein B and Kinzler KW.2004. Cancer genes and the pathways they control[J].Nature Medicine,10:789-799.
Volinia S, Calin GA, Liu CG, et al.2006a. A microRNA expression signature of human solid tumors defines cancer gene targets[J]. Proceedings of the National Academy of Sciences of the United States of America,103:2257-2261.
Volinia S, Calin GA, Liu CG, et al.2006b. A microRNA expression signature of human solid tumors defines cancer gene targets[J]. Proc Natl Acad Sci U S A,103:2257-2261.
Voorhoeve PM, le Sage C, Schrier M, et al.2006. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors[J]. Cell,124:1169-1181.
Wang G, Mao W and Zheng S.2008. MicroRNA-183 regulates Ezrin expression in lung cancer cells[J]. FEBS Lett,582:3663-3668.
Wang Z and Burke PA.2013. The role of microRNAs in hepatocyte nuclear factor-4alpha expression and transactivation[J]. Biochim Biophys Acta,1829:436-442.
Watt AJ, Garrison WD and Duncan SA.2003. HNF4:a central regulator of hepatocyte differentiation and function[J]. Hepatology,37:1249-1253.
Wei J, Gao W, Zhu CJ, et al.2011. Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer[J]. Chin J Cancer,30:407-414.
Weiler J, Hunziker J and Hall J.2006. Anti-miRNA oligonucleotides (AMOs):ammunition to target miRNAs implicated in human disease?[J]. Gene Ther,13:496-502.
Welch C, Chen Y and Stallings RL.2007. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells[J]. Oncogene,26:5017-5022.
Wendler A, Keller D, Albrecht C, et al.2011. Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells[J]. Oncol Rep,25:273-279.
Wightman B, Burglin TR, Gatto J, et al.1991. Negative regulatory sequences in the lin-14 3'-untranslated region are necessary to generate a temporal switch during Caenorhabditis elegans development[J]. Genes Dev,5:1813-1824.
Wightman B, Ha I and Ruvkun G.1993. Posttranscriptional Regulation of the Heterochronic Gene Lin-14 by Lin-4 Mediates Temporal Pattern-Formation in C-Elegans[J]. Cell,75:855-862.
Wolterbeek APM, Schoevers EJ, Rutten AAJJL, et al.1995. A Critical-Appraisal of Intratracheal Instillation of Benzo[a]Pyrene to Syrian Golden-Hamsters as a Model in Respiratory-Tract Carcinogenesis[J]. Cancer Lett,89:107-116.
Wu L and Belasco JG.2008. Let me count the ways:Mechanisms of gene regulation by miRNAs and siRNAs[J]. Mol Cell,29:1-7.
Wu LG, Fan JH and Belasco JG.2006. MicroRNAs direct rapid deadenylation of mRNA[J]. Proceedings of the National Academy of Sciences of the United States of America, 103:4034-4039.
Wu LZ, Timmers C, Maiti B, et al.2001. The E2F1-3 transcription factors are essential for cellular proliferation[J]. Nature,414:457-462.
Wu Q, Jin HF, Yang ZP, et al.2010. MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2[J]. Biochem Biophys Res Commun,392:340-345.
Xi Y, Formentini A, Chien M, et al.2006. Prognostic Values of microRNAs in Colorectal Cancer[J]. Biomark Insights,2:113-121.
Xiao BX, Guo JM, Miao Y, et al.2009. Detection of miR-106a in gastric carcinoma and its clinical significance[J]. Clinica Chimica Acta,400:97-102.
Xie Y, Todd NW, Liu Z, et al.2010. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer[J]. Lung Cancer,67:170-176.
Yanaihara N, Caplen N, Bowman E, et al.2006a. Unique MicroRNA molecular profiles in lung cancer diagnosis and prognosis[J]. Toxicologic Pathology,34:1017-1018.
Yanaihara N, Caplen N, Bowman E, et al.2006b. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis[J]. Cancer Cell,9:189-198.
Yang XJ, Feng M, Jiang X, et al.2009. miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A[J]. Genes Dev,23:2388-2393.
Yang Y, Li XF, Yang Q, et al.2010. The role of microRNA in human lung squamous cell carcinoma[J]. Cancer Genetics and Cytogenetics,200:127-133.
Yu F, Yao H, Zhu P, et al.2007. let-7 regulates self renewal and tumorigenicity of breast cancer cells[J].Cell,131:1109-1123.
Yu SL, Chen HY, Chang GC, et al.2008a. MicroRNA signature predicts survival and relapse in lung cancer[J]. Cancer Cell,13:48-57.
Yu SL, Chen HY, Chang GC, et al.2008b. MicroRNA signature predicts survival and relapse in lung cancer[J]. Cancer Cell,13:48-57.
Zhang BH, Pan XP, Cobb GP, et al.2007. microRNAs as oncogenes and tumor suppressors[J]. Developmental Biology,302:1-12.
Zhang JG, Wang JJ, Zhao F, et al.2010. MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC)[J]. Clinica Chimica Acta,411:846-852.
Zhao Y, Wang SX, Aunan K, et al.2006. Air pollution and lung cancer risks in China-a meta-analysis[J]. Science of the Total Environment,366:500-513.
Zhao YC, Deng CS, Wang JR, et al.2011. Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer[J]. Breast Cancer Res Treat,127:69-80.
Zhu S, Si ML, Wu H, et al.2007. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1)[J].J Biol Chem,282:14328-14336.