miRNA在调控恶性肿瘤细胞的恶性进展中的作用研究
|
摘要
肝癌和乳腺癌都是常见的恶性肿瘤,其常发现有miRNA的失调。miRNA是一种种类众多的约22个碱基的非编码小RNA,其通过降解靶标基因的mRNA或抑制翻译来调控其标靶基因的表达。本文,我们发现miRNA与肝癌和乳腺癌的恶性进展密切相关。
癌症迁移是肝癌患者因癌死亡的主要原因,而研究发现miRNA可以调控癌症的迁移。有研究表明miR-198在肝癌组织中下调,但是其在肝癌中的功能并不清楚。本文中,我们发现miR-198可以通过抑制原癌基因c-MET的3端非编码区的翻译活性。过表达miR-198可以抑制c-MET基因的表达,且会抑制HGF作用下的HGF/c-MET信号通路下游的p44/42 MAPK活性,从而抑制HGF诱导的肝癌细胞迁移与侵袭。综上所述,miR-198可通过抑制HGF/c-MET信号途径抑制肝癌细胞的的转移与侵袭。
雌激素是一种固醇类激素,其以雌激素受体依赖的方式调节细胞的生存与增值,密切影响着女性乳腺癌患者的病情发展。本文中,我们通过TaqMan实时定量PCR实验发现雌激素以雌激素受体依赖的方式抑制miR-26的表达水平,恢复miR-26的表达后能明显抑制雌激素诱导的乳腺癌细胞生长。miR-26可以通过结合到GREB1基因3端非编码抑制其表达,这也是miR-26抑制雌激素诱导的乳腺癌细胞生长的重要原因。总之,miR-26表达水平的改变与雌激素诱导的乳腺癌细胞生长密切相关,也为理解抗雌激素治疗的耐药提供了新的思路。
Liver and breast cancers are among the leading deadly types of cancer. Altered expression of microRNAs (miRNA), an abundant class of about 22nt noncoding RNAs that mostly function as negative regulators of gene expression by directly degrading messenger RNA (mRNA) or repressing protein translation, is common in Liver and breast cancer. In this study, we demonstrate that miRNA is closely involved in the progression of Liver and breast cancers.
Meastasis is the leading cause of death in patients with hepatocellular carcinoma (HCC) and microRNAs have been implicated to influence this process. Emerging evidence indicates that miR-198 is down-regulated in HCC compared to normal liver parenchyma, but the functional roles of miR-198 in HCC cells remains unexplored. Herein, we show that miR-198 directly targets c-MET via its 3’UTR. Forced expression of miR-198 decreased c-MET expression at both mRNA and protein levels and consequently diminished HGF induced phosphorylation of p44/42 MAPK in HCC cells. Forced expression of miR-198 inhibited HGF promotion of HCC cell migration and invasion in a c-MET dependent manner. In conclusion, we have identified miR-198 as a novel suppressor of HCC cell invasion by negative regulation of the HGF/c-MET pathway.
The steroid hormone estrogen is closely involved in the development and progression of women breast cancer through its effects on cellular processed including cell survival and proliferation, and that is acting via the estrogen receptors. Here, we analyze the regulation of miR-26 expression in response to estrogen, by using miRNA TaqMan real-time reverse transcription-PCR experiments, we show that the expression of miR-26a and miR-26b decreases following estrogen treatment in an ER-dependent manner. We further show that enforced expression of miR-26 reduces estrogen-dependent cell growth, which was associated with suppressing the expression of GREB1. we show that miR-26 directly targets GREB1 via its 3’UTR. Forced expression of miR-26 decreased GREB1protein expression. Overall, our data indicate that the alteration of miR-26 expression in response to estrogen play a key role in estrogen-dependent cell growth and indicate the role of miR-26 in the understanding of anti-estrogen resistance of breast cancer.
癌症迁移是肝癌患者因癌死亡的主要原因,而研究发现miRNA可以调控癌症的迁移。有研究表明miR-198在肝癌组织中下调,但是其在肝癌中的功能并不清楚。本文中,我们发现miR-198可以通过抑制原癌基因c-MET的3端非编码区的翻译活性。过表达miR-198可以抑制c-MET基因的表达,且会抑制HGF作用下的HGF/c-MET信号通路下游的p44/42 MAPK活性,从而抑制HGF诱导的肝癌细胞迁移与侵袭。综上所述,miR-198可通过抑制HGF/c-MET信号途径抑制肝癌细胞的的转移与侵袭。
雌激素是一种固醇类激素,其以雌激素受体依赖的方式调节细胞的生存与增值,密切影响着女性乳腺癌患者的病情发展。本文中,我们通过TaqMan实时定量PCR实验发现雌激素以雌激素受体依赖的方式抑制miR-26的表达水平,恢复miR-26的表达后能明显抑制雌激素诱导的乳腺癌细胞生长。miR-26可以通过结合到GREB1基因3端非编码抑制其表达,这也是miR-26抑制雌激素诱导的乳腺癌细胞生长的重要原因。总之,miR-26表达水平的改变与雌激素诱导的乳腺癌细胞生长密切相关,也为理解抗雌激素治疗的耐药提供了新的思路。
Liver and breast cancers are among the leading deadly types of cancer. Altered expression of microRNAs (miRNA), an abundant class of about 22nt noncoding RNAs that mostly function as negative regulators of gene expression by directly degrading messenger RNA (mRNA) or repressing protein translation, is common in Liver and breast cancer. In this study, we demonstrate that miRNA is closely involved in the progression of Liver and breast cancers.
Meastasis is the leading cause of death in patients with hepatocellular carcinoma (HCC) and microRNAs have been implicated to influence this process. Emerging evidence indicates that miR-198 is down-regulated in HCC compared to normal liver parenchyma, but the functional roles of miR-198 in HCC cells remains unexplored. Herein, we show that miR-198 directly targets c-MET via its 3’UTR. Forced expression of miR-198 decreased c-MET expression at both mRNA and protein levels and consequently diminished HGF induced phosphorylation of p44/42 MAPK in HCC cells. Forced expression of miR-198 inhibited HGF promotion of HCC cell migration and invasion in a c-MET dependent manner. In conclusion, we have identified miR-198 as a novel suppressor of HCC cell invasion by negative regulation of the HGF/c-MET pathway.
The steroid hormone estrogen is closely involved in the development and progression of women breast cancer through its effects on cellular processed including cell survival and proliferation, and that is acting via the estrogen receptors. Here, we analyze the regulation of miR-26 expression in response to estrogen, by using miRNA TaqMan real-time reverse transcription-PCR experiments, we show that the expression of miR-26a and miR-26b decreases following estrogen treatment in an ER-dependent manner. We further show that enforced expression of miR-26 reduces estrogen-dependent cell growth, which was associated with suppressing the expression of GREB1. we show that miR-26 directly targets GREB1 via its 3’UTR. Forced expression of miR-26 decreased GREB1protein expression. Overall, our data indicate that the alteration of miR-26 expression in response to estrogen play a key role in estrogen-dependent cell growth and indicate the role of miR-26 in the understanding of anti-estrogen resistance of breast cancer.
引文
Abelson, J. F., Kwan, K. Y., O'Roak, B. J., Baek, D. Y., Stillman, A. A., Morgan, T. M., Mathews, C. A., Pauls, D. L., Rasin, M. R., Gunel, M., et al. (2005). Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317-320.
Adams, B. D., Furneaux, H., and White, B. A. (2007). The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. Mol Endocrinol 21, 1132-1147.
Asangani, I. A., Rasheed, S. A., Nikolova, D. A., Leupold, J. H., Colburn, N. H., Post, S., and Allgayer, H. (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27, 2128-2136.
Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233. Benvenuti, S., and Comoglio, P. M. (2007). The MET receptor tyrosine kinase in invasion and metastasis. J Cell Physiol 213, 316-325.
Bissell, M. J., and Radisky, D. (2001). Putting tumours in context. Nat Rev Cancer 1, 46-54. Blenkiron, C., Goldstein, L. D., Thorne, N. P., Spiteri, I., Chin, S. F., Dunning, M. J., Barbosa-Morais, N. L., Teschendorff, A. E., Green, A. R., Ellis, I. O., et al. (2007). MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 8, R214.
Bommer, G. T., Gerin, I., Feng, Y., Kaczorowski, A. J., Kuick, R., Love, R. E., Zhai, Y., Giordano, T. J., Qin, Z. S., Moore, B. B., et al. (2007). p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 17, 1298-1307.
Bonci, D., Coppola, V., Musumeci, M., Addario, A., Giuffrida, R., Memeo, L., D'Urso, L., Pagliuca, A., Biffoni, M., Labbaye, C., et al. (2008). The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14, 1271-1277.
Bosch, F. X., Ribes, J., Diaz, M., and Cleries, R. (2004). Primary liver cancer: worldwide incidence and trends. Gastroenterology 127, S5-S16.
Bottaro, D. P., Rubin, J. S., Faletto, D. L., Chan, A. M., Kmiecik, T. E., Vande Woude, G. F., and Aaronson, S. A. (1991). Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251, 802-804.
Bottoni, A., Piccin, D., Tagliati, F., Luchin, A., Zatelli, M. C., and degli Uberti, E. C. (2005). miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol 204, 280-285.
Brennecke, J., Stark, A., Russell, R. B., and Cohen, S. M. (2005). Principles of microRNA-target recognition. PLoS Biol 3, e85.
Calin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K., et al. (2002). Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99, 15524-15529.
Calin, G. A., Ferracin, M., Cimmino, A., Di Leva, G., Shimizu, M., Wojcik, S. E., Iorio, M. V., Visone, R., Sever, N. I., Fabbri, M., et al. (2005). A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353, 1793-1801.
Campbell, P. J., Pleasance, E. D., Stephens, P. J., Dicks, E., Rance, R., Goodhead, I., Follows, G. A., Green, A. R., Futreal, P. A., and Stratton, M. R. (2008a). Subclonal phylogenetic structures in cancerrevealed by ultra-deep sequencing. Proc Natl Acad Sci U S A 105, 13081-13086.
Campbell, P. J., Stephens, P. J., Pleasance, E. D., O'Meara, S., Li, H., Santarius, T., Stebbings, L. A., Leroy, C., Edkins, S., Hardy, C., et al. (2008b). Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat Genet 40, 722-729.
Cecchi, F., Rabe, D. C., and Bottaro, D. P. (2010). Targeting the HGF/Met signalling pathway in cancer. Eur J Cancer 46, 1260-1270.
Chan, J. A., Krichevsky, A. M., and Kosik, K. S. (2005). MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65, 6029-6033.
Chang, T. C., Wentzel, E. A., Kent, O. A., Ramachandran, K., Mullendore, M., Lee, K. H., Feldmann, G., Yamakuchi, M., Ferlito, M., Lowenstein, C. J., et al. (2007). Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26, 745-752.
Chirgadze, D. Y., Hepple, J., Byrd, R. A., Sowdhamini, R., Blundell, T. L., and Gherardi, E. (1998). Insights into the structure of hepatocyte growth factor/scatter factor (HGF/SF) and implications for receptor activation. FEBS Lett 430, 126-129.
Chiyomaru, T., Enokida, H., Tatarano, S., Kawahara, K., Uchida, Y., Nishiyama, K., Fujimura, L., Kikkawa, N., Seki, N., and Nakagawa, M. (2010). miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer 102, 883-891.
Cho, W. C., Chow, A. S., and Au, J. S. (2011). MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1. RNA Biol 8.
Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., Wojcik, S. E., Aqeilan, R. I., Zupo, S., Dono, M., et al. (2005). miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102, 13944-13949.
Comoglio, P. M., Giordano, S., and Trusolino, L. (2008). Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 7, 504-516.
Cooper, C. S., Park, M., Blair, D. G., Tainsky, M. A., Huebner, K., Croce, C. M., and Vande Woude, G. F. (1984). Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311, 29-33.
Corsten, M. F., Miranda, R., Kasmieh, R., Krichevsky, A. M., Weissleder, R., and Shah, K. (2007). MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res 67, 8994-9000.
Craig, V. J., Cogliatti, S. B., Imig, J., Renner, C., Neuenschwander, S., Rehrauer, H., Schlapbach, R., Dirnhofer, S., Tzankov, A., and Muller, A. (2011). Myc-mediated repression of microRNA-34a promotes high grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood.
Deschenes, J., Bourdeau, V., White, J. H., and Mader, S. (2007). Regulation of GREB1 transcription by estrogen receptor alpha through a multipartite enhancer spread over 20 kb of upstream flanking sequences. J Biol Chem 282, 17335-17339.
Ding, J., Huang, S., Wu, S., Zhao, Y., Liang, L., Yan, M., Ge, C., Yao, J., Chen, T., Wan, D., et al. (2010). Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nat Cell Biol 12, 390-399.
Dohner, H., Stilgenbauer, S., Benner, A., Leupolt, E., Krober, A., Bullinger, L., Dohner, K., Bentz, M., and Lichter, P. (2000). Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343, 1910-1916.
Eads, C. A., Danenberg, K. D., Kawakami, K., Saltz, L. B., Danenberg, P. V., and Laird, P. W. (1999). CpG island hypermethylation in human colorectal tumors is not associated with DNAmethyltransferase overexpression. Cancer Res 59, 2302-2306.
El-Serag, H. B., and Rudolph, K. L. (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132, 2557-2576.
Esquela-Kerscher, A., and Slack, F. J. (2006). Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 6, 259-269.
Eyholzer, M., Schmid, S., Wilkens, L., Mueller, B. U., and Pabst, T. (2010). The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML. Br J Cancer 103, 275-284.
Fabbri, M., Garzon, R., Cimmino, A., Liu, Z., Zanesi, N., Callegari, E., Liu, S., Alder, H., Costinean, S., Fernandez-Cymering, C., et al. (2007). MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 104, 15805-15810.
Filipowicz, W., Bhattacharyya, S. N., and Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9, 102-114.
Fisher, B., Dignam, J., Bryant, J., DeCillis, A., Wickerham, D. L., Wolmark, N., Costantino, J., Redmond, C., Fisher, E. R., Bowman, D. M., et al. (1996). Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 88, 1529-1542.
Flynt, A. S., and Lai, E. C. (2008). Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 9, 831-842.
Fornari, F., Gramantieri, L., Ferracin, M., Veronese, A., Sabbioni, S., Calin, G. A., Grazi, G. L., Giovannini, C., Croce, C. M., Bolondi, L., and Negrini, M. (2008). MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 27, 5651-5661.
Forner, A., Hessheimer, A. J., Isabel Real, M., and Bruix, J. (2006). Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol 60, 89-98.
Garofalo, M., Di Leva, G., Romano, G., Nuovo, G., Suh, S. S., Ngankeu, A., Taccioli, C., Pichiorri, F., Alder, H., Secchiero, P., et al. (2009). miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell 16, 498-509.
Garzon, R., Liu, S., Fabbri, M., Liu, Z., Heaphy, C. E., Callegari, E., Schwind, S., Pang, J., Yu, J., Muthusamy, N., et al. (2009). MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113, 6411-6418.
Ghosh, M. G., Thompson, D. A., and Weigel, R. J. (2000). PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer. Cancer Res 60, 6367-6375.
Gramantieri, L., Ferracin, M., Fornari, F., Veronese, A., Sabbioni, S., Liu, C. G., Calin, G. A., Giovannini, C., Ferrazzi, E., Grazi, G. L., et al. (2007). Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res 67, 6092-6099.
Gregersen, L. H., Jacobsen, A. B., Frankel, L. B., Wen, J., Krogh, A., and Lund, A. H. (2010). MicroRNA-145 targets YES and STAT1 in colon cancer cells. PLoS One 5, e8836.
Guo, Y., Chen, Z., Zhang, L., Zhou, F., Shi, S., Feng, X., Li, B., Meng, X., Ma, X., Luo, M., et al. (2008). Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res 68, 26-33.
Hammond, S. M., Bernstein, E., Beach, D., and Hannon, G. J. (2000). An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404, 293-296.
Hanahan, D., and Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674.
Harvey, J. M., Clark, G. M., Osborne, C. K., and Allred, D. C. (1999). Estrogen receptor status byimmunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17, 1474-1481.
Hayashita, Y., Osada, H., Tatematsu, Y., Yamada, H., Yanagisawa, K., Tomida, S., Yatabe, Y., Kawahara, K., Sekido, Y., and Takahashi, T. (2005). A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65, 9628-9632.
He, L., He, X., Lim, L. P., de Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., et al. (2007). A microRNA component of the p53 tumour suppressor network. Nature 447, 1130-1134.
He, L., Thomson, J. M., Hemann, M. T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S. W., Hannon, G. J., and Hammond, S. M. (2005). A microRNA polycistron as a potential human oncogene. Nature 435, 828-833.
Hou, J., Lin, L., Zhou, W., Wang, Z., Ding, G., Dong, Q., Qin, L., Wu, X., Zheng, Y., Yang, Y., et al. (2011). Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell 19, 232-243.
Iorio, M. V., Ferracin, M., Liu, C. G., Veronese, A., Spizzo, R., Sabbioni, S., Magri, E., Pedriali, M., Fabbri, M., Campiglio, M., et al. (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65, 7065-7070.
Iorio, M. V., Visone, R., Di Leva, G., Donati, V., Petrocca, F., Casalini, P., Taccioli, C., Volinia, S., Liu, C. G., Alder, H., et al. (2007). MicroRNA signatures in human ovarian cancer. Cancer Res 67, 8699-8707.
Jaiyesimi, I. A., Buzdar, A. U., Decker, D. A., and Hortobagyi, G. N. (1995). Use of tamoxifen for breast cancer: twenty-eight years later. J Clin Oncol 13, 513-529.
Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., and Slack, F. J. (2005). RAS is regulated by the let-7 microRNA family. Cell 120, 635-647.
Johnston, R. J., and Hobert, O. (2003). A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426, 845-849.
Jones, P. A., and Laird, P. W. (1999). Cancer epigenetics comes of age. Nat Genet 21, 163-167.
Jopling, C. L., Yi, M., Lancaster, A. M., Lemon, S. M., and Sarnow, P. (2005). Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309, 1577-1581.
Kanai, Y., and Hirohashi, S. (2007). Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis 28, 2434-2442.
Kent, O. A., Chivukula, R. R., Mullendore, M., Wentzel, E. A., Feldmann, G., Lee, K. H., Liu, S., Leach, S. D., Maitra, A., and Mendell, J. T. (2010). Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev 24, 2754-2759.
Ketting, R. F., Fischer, S. E., Bernstein, E., Sijen, T., Hannon, G. J., and Plasterk, R. H. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15, 2654-2659.
Kim, H., Kwon, Y. M., Kim, J. S., Han, J., Shim, Y. M., Park, J., and Kim, D. H. (2006). Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancer. Cancer 107, 1042-1049.
Kim, V. N. (2004). MicroRNA precursors in motion: exportin-5 mediates their nuclear export. Trends Cell Biol 14, 156-159.
Kim, Y. K., and Kim, V. N. (2007). Processing of intronic microRNAs. EMBO J 26, 775-783.
Kondo, N., Toyama, T., Sugiura, H., Fujii, Y., and Yamashita, H. (2008). miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res 68, 5004-5008.
Lawrie, C. H., Soneji, S., Marafioti, T., Cooper, C. D., Palazzo, S., Paterson, J. C., Cattan, H., Enver, T., Mager, R., Boultwood, J., et al. (2007). MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer 121, 1156-1161.
Lecellier, C. H., Dunoyer, P., Arar, K., Lehmann-Che, J., Eyquem, S., Himber, C., Saib, A., and Voinnet, O. (2005). A cellular microRNA mediates antiviral defense in human cells. Science 308, 557-560.
Lee, R. C., Feinbaum, R. L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854.
Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Radmark, O., Kim, S., and Kim, V. N. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415-419.
Lee, Y., Jeon, K., Lee, J. T., Kim, S., and Kim, V. N. (2002). MicroRNA maturation: stepwise processing and subcellular localization. EMBO J 21, 4663-4670.
Lewis, B. P., Burge, C. B., and Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20.
Linsley, P. S., Schelter, J., Burchard, J., Kibukawa, M., Martin, M. M., Bartz, S. R., Johnson, J. M., Cummins, J. M., Raymond, C. K., Dai, H., et al. (2007). Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol 27, 2240-2252.
Liu, C., Kelnar, K., Liu, B., Chen, X., Calhoun-Davis, T., Li, H., Patrawala, L., Yan, H., Jeter, C., Honorio, S., et al. (2011). The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17, 211-215.
Lu, S., and Cullen, B. R. (2004). Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and MicroRNA biogenesis. J Virol 78, 12868-12876.
Ma, L., Teruya-Feldstein, J., and Weinberg, R. A. (2007). Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682-688.
Maillot, G., Lacroix-Triki, M., Pierredon, S., Gratadou, L., Schmidt, S., Benes, V., Roche, H., Dalenc, F., Auboeuf, D., Millevoi, S., and Vagner, S. (2009). Widespread estrogen-dependent repression of micrornas involved in breast tumor cell growth. Cancer Res 69, 8332-8340.
Meng, F., Henson, R., Wehbe-Janek, H., Ghoshal, K., Jacob, S. T., and Patel, T. (2007). MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133, 647-658.
Meng, Z., Fu, X., Chen, X., Zeng, S., Tian, Y., Jove, R., Xu, R., and Huang, W. (2010). miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice. Hepatology 52, 2148-2157.
Michael, M. Z., SM, O. C., van Holst Pellekaan, N. G., Young, G. P., and James, R. J. (2003). Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1, 882-891.
Motoyama, K., Inoue, H., Nakamura, Y., Uetake, H., Sugihara, K., and Mori, M. (2008). Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res 14, 2334-2340.
Mott, J. L., Kobayashi, S., Bronk, S. F., and Gores, G. J. (2007). mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 26, 6133-6140.
Mott, J. L., Kurita, S., Cazanave, S. C., Bronk, S. F., Werneburg, N. W., and Fernandez-Zapico, M. E.(2010). Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB. J Cell Biochem 110, 1155-1164.
Murakami, Y., Yasuda, T., Saigo, K., Urashima, T., Toyoda, H., Okanoue, T., and Shimotohno, K. (2006). Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 25, 2537-2545.
Musgrove, E. A., and Sutherland, R. L. (2009). Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 9, 631-643.
Muss, H. B. (1992). Endocrine therapy for advanced breast cancer: a review. Breast Cancer Res Treat 21, 15-26.
Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science 194, 23-28. O'Donnell, K. A., Wentzel, E. A., Zeller, K. I., Dang, C. V., and Mendell, J. T. (2005). c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839-843.
Ota, A., Tagawa, H., Karnan, S., Tsuzuki, S., Karpas, A., Kira, S., Yoshida, Y., and Seto, M. (2004). Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res 64, 3087-3095.
Ozaki, I., Mizuta, T., Zhao, G., Zhang, H., Yoshimura, T., Kawazoe, S., Eguchi, Y., Yasutake, T., Hisatomi, A., Sakai, T., and Yamamoto, K. (2003). Induction of multiple matrix metalloproteinase genes in human hepatocellular carcinoma by hepatocyte growth factor via a transcription factor Ets-1. Hepatol Res 27, 289-301.
Ozsolak, F., Poling, L. L., Wang, Z., Liu, H., Liu, X. S., Roeder, R. G., Zhang, X., Song, J. S., and Fisher, D. E. (2008). Chromatin structure analyses identify miRNA promoters. Genes Dev 22, 3172-3183.
Park, M., Dean, M., Cooper, C. S., Schmidt, M., O'Brien, S. J., Blair, D. G., and Vande Woude, G. F. (1986). Mechanism of met oncogene activation. Cell 45, 895-904.
Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., Maller, B., Hayward, D. C., Ball, E. E., Degnan, B., Muller, P., et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408, 86-89.
Patra, S. K., Patra, A., Zhao, H., and Dahiya, R. (2002). DNA methyltransferase and demethylase in human prostate cancer. Mol Carcinog 33, 163-171.
Pekarsky, Y., Santanam, U., Cimmino, A., Palamarchuk, A., Efanov, A., Maximov, V., Volinia, S., Alder, H., Liu, C. G., Rassenti, L., et al. (2006). Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res 66, 11590-11593.
Petrocca, F., Visone, R., Onelli, M. R., Shah, M. H., Nicoloso, M. S., de Martino, I., Iliopoulos, D., Pilozzi, E., Liu, C. G., Negrini, M., et al. (2008). E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13, 272-286.
Pineau, P., Volinia, S., McJunkin, K., Marchio, A., Battiston, C., Terris, B., Mazzaferro, V., Lowe, S. W., Croce, C. M., and Dejean, A. (2010). miR-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci U S A 107, 264-269.
Poy, M. N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., Macdonald, P. E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., and Stoffel, M. (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226-230.
Qian, C. N., Guo, X., Cao, B., Kort, E. J., Lee, C. C., Chen, J., Wang, L. M., Mai, W. Y., Min, H. Q., Hong, M. H., et al. (2002). Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma. Cancer Res 62, 589-596.
Rajewsky, N. (2006). microRNA target predictions in animals. Nat Genet 38 Suppl, S8-13.
Raveche, E. S., Salerno, E., Scaglione, B. J., Manohar, V., Abbasi, F., Lin, Y. C., Fredrickson, T., Landgraf, P., Ramachandra, S., Huppi, K., et al. (2007). Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood 109, 5079-5086.
Raver-Shapira, N., Marciano, E., Meiri, E., Spector, Y., Rosenfeld, N., Moskovits, N., Bentwich, Z., and Oren, M. (2007). Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 26, 731-743.
Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., Bettinger, J. C., Rougvie, A. E., Horvitz, H. R., and Ruvkun, G. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901-906.
Roldo, C., Missiaglia, E., Hagan, J. P., Falconi, M., Capelli, P., Bersani, S., Calin, G. A., Volinia, S., Liu, C. G., Scarpa, A., and Croce, C. M. (2006). MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 24, 4677-4684.
Sachdeva, M., and Mo, Y. Y. (2010). MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res 70, 378-387.
Sachdeva, M., Zhu, S., Wu, F., Wu, H., Walia, V., Kumar, S., Elble, R., Watabe, K., and Mo, Y. Y. (2009). p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A 106, 3207-3212.
Schepeler, T., Reinert, J. T., Ostenfeld, M. S., Christensen, L. L., Silahtaroglu, A. N., Dyrskjot, L., Wiuf, C., Sorensen, F. J., Kruhoffer, M., Laurberg, S., et al. (2008). Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res 68, 6416-6424.
Schetter, A. J., Leung, S. Y., Sohn, J. J., Zanetti, K. A., Bowman, E. D., Yanaihara, N., Yuen, S. T., Chan, T. L., Kwong, D. L., Au, G. K., et al. (2008). MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 299, 425-436.
Scott, G. K., Goga, A., Bhaumik, D., Berger, C. E., Sullivan, C. S., and Benz, C. C. (2007). Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 282, 1479-1486.
Seike, M., Goto, A., Okano, T., Bowman, E. D., Schetter, A. J., Horikawa, I., Mathe, E. A., Jen, J., Yang, P., Sugimura, H., et al. (2009). MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci U S A 106, 12085-12090.
Selbach, M., Schwanhausser, B., Thierfelder, N., Fang, Z., Khanin, R., and Rajewsky, N. (2008). Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58-63.
Sherman, M. (2005). Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 25, 143-154.
Si, M. L., Zhu, S., Wu, H., Lu, Z., Wu, F., and Mo, Y. Y. (2007). miR-21-mediated tumor growth. Oncogene 26, 2799-2803.
Simpson, E. R., Misso, M., Hewitt, K. N., Hill, R. A., Boon, W. C., Jones, M. E., Kovacic, A., Zhou, J., and Clyne, C. D. (2005). Estrogen--the good, the bad, and the unexpected. Endocr Rev 26, 322-330. Sipeki, S., Bander, E., Buday, L., Farkas, G., Bacsy, E., Ways, D. K., and Farago, A. (1999).
Phosphatidylinositol 3-kinase contributes to Erk1/Erk2 MAP kinase activation associated with hepatocyte growth factor-induced cell scattering. Cell Signal 11, 885-890.
Sun, J., Nawaz, Z., and Slingerland, J. M. (2007). Long-range activation of GREB1 by estrogen receptor via three distal consensus estrogen-responsive elements in breast cancer cells. Mol Endocrinol21, 2651-2662.
Takamizawa, J., Konishi, H., Yanagisawa, K., Tomida, S., Osada, H., Endoh, H., Harano, T., Yatabe, Y., Nagino, M., Nimura, Y., et al. (2004). Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64, 3753-3756.
Tarasov, V., Jung, P., Verdoodt, B., Lodygin, D., Epanchintsev, A., Menssen, A., Meister, G., and Hermeking, H. (2007). Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6, 1586-1593.
Tavazoie, S. F., Alarcon, C., Oskarsson, T., Padua, D., Wang, Q., Bos, P. D., Gerald, W. L., and Massague, J. (2008). Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451, 147-152.
Tay, Y., Zhang, J., Thomson, A. M., Lim, B., and Rigoutsos, I. (2008). MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455, 1124-1128.
Tazawa, H., Tsuchiya, N., Izumiya, M., and Nakagama, H. (2007). Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A 104, 15472-15477.
Thum, T., Catalucci, D., and Bauersachs, J. (2008). MicroRNAs: novel regulators in cardiac development and disease. Cardiovasc Res 79, 562-570.
Trusolino, L., Bertotti, A., and Comoglio, P. M. (2010). MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 11, 834-848.
Tulasne, D., and Foveau, B. (2008). The shadow of death on the MET tyrosine kinase receptor. Cell Death Differ 15, 427-434.
Vargo-Gogola, T., and Rosen, J. M. (2007). Modelling breast cancer: one size does not fit all. Nat Rev Cancer 7, 659-672.
Varnholt, H. (2008). The role of microRNAs in primary liver cancer. Ann Hepatol 7, 104-113.
Wang, S., Bian, C., Yang, Z., Bo, Y., Li, J., Zeng, L., Zhou, H., and Zhao, R. C. (2009). miR-145 inhibits breast cancer cell growth through RTKN. Int J Oncol 34, 1461-1466.
Whittaker, S., Marais, R., and Zhu, A. X. (2010). The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 29, 4989-5005.
Wojta, J., Kaun, C., Breuss, J. M., Koshelnick, Y., Beckmann, R., Hattey, E., Mildner, M., Weninger, W., Nakamura, T., Tschachler, E., and Binder, B. R. (1999). Hepatocyte growth factor increases expression of vascular endothelial growth factor and plasminogen activator inhibitor-1 in human keratinocytes and the vascular endothelial growth factor receptor flk-1 in human endothelial cells. Lab Invest 79, 427-438.
Xie, X., Lu, J., Kulbokas, E. J., Golub, T. R., Mootha, V., Lindblad-Toh, K., Lander, E. S., and Kellis, M. (2005). Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals. Nature 434, 338-345.
Xiong, Y., Fang, J. H., Yun, J. P., Yang, J., Zhang, Y., Jia, W. H., and Zhuang, S. M. (2010). Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology 51, 836-845.
Xu, P., Vernooy, S. Y., Guo, M., and Hay, B. A. (2003). The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol 13, 790-795.
You, W. K., and McDonald, D. M. (2008). The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Rep 41, 833-839.
Yu, F., Yao, H., Zhu, P., Zhang, X., Pan, Q., Gong, C., Huang, Y., Hu, X., Su, F., Lieberman, J., and
Song, E. (2007). let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131, 1109-1123.
Zeng, Y., and Cullen, B. R. (2004). Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res 32, 4776-4785.
Zeng, Y., Yi, R., and Cullen, B. R. (2005). Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J 24, 138-148.
Zhao, J. J., Lin, J., Lwin, T., Yang, H., Guo, J., Kong, W., Dessureault, S., Moscinski, L. C., Rezania, D., Dalton, W. S., et al. (2010). microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood 115, 2630-2639.
Zhu, S., Si, M. L., Wu, H., and Mo, Y. Y. (2007). MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282, 14328-14336.
Adams, B. D., Furneaux, H., and White, B. A. (2007). The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. Mol Endocrinol 21, 1132-1147.
Asangani, I. A., Rasheed, S. A., Nikolova, D. A., Leupold, J. H., Colburn, N. H., Post, S., and Allgayer, H. (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27, 2128-2136.
Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233. Benvenuti, S., and Comoglio, P. M. (2007). The MET receptor tyrosine kinase in invasion and metastasis. J Cell Physiol 213, 316-325.
Bissell, M. J., and Radisky, D. (2001). Putting tumours in context. Nat Rev Cancer 1, 46-54. Blenkiron, C., Goldstein, L. D., Thorne, N. P., Spiteri, I., Chin, S. F., Dunning, M. J., Barbosa-Morais, N. L., Teschendorff, A. E., Green, A. R., Ellis, I. O., et al. (2007). MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 8, R214.
Bommer, G. T., Gerin, I., Feng, Y., Kaczorowski, A. J., Kuick, R., Love, R. E., Zhai, Y., Giordano, T. J., Qin, Z. S., Moore, B. B., et al. (2007). p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 17, 1298-1307.
Bonci, D., Coppola, V., Musumeci, M., Addario, A., Giuffrida, R., Memeo, L., D'Urso, L., Pagliuca, A., Biffoni, M., Labbaye, C., et al. (2008). The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 14, 1271-1277.
Bosch, F. X., Ribes, J., Diaz, M., and Cleries, R. (2004). Primary liver cancer: worldwide incidence and trends. Gastroenterology 127, S5-S16.
Bottaro, D. P., Rubin, J. S., Faletto, D. L., Chan, A. M., Kmiecik, T. E., Vande Woude, G. F., and Aaronson, S. A. (1991). Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251, 802-804.
Bottoni, A., Piccin, D., Tagliati, F., Luchin, A., Zatelli, M. C., and degli Uberti, E. C. (2005). miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol 204, 280-285.
Brennecke, J., Stark, A., Russell, R. B., and Cohen, S. M. (2005). Principles of microRNA-target recognition. PLoS Biol 3, e85.
Calin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K., et al. (2002). Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99, 15524-15529.
Calin, G. A., Ferracin, M., Cimmino, A., Di Leva, G., Shimizu, M., Wojcik, S. E., Iorio, M. V., Visone, R., Sever, N. I., Fabbri, M., et al. (2005). A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353, 1793-1801.
Campbell, P. J., Pleasance, E. D., Stephens, P. J., Dicks, E., Rance, R., Goodhead, I., Follows, G. A., Green, A. R., Futreal, P. A., and Stratton, M. R. (2008a). Subclonal phylogenetic structures in cancerrevealed by ultra-deep sequencing. Proc Natl Acad Sci U S A 105, 13081-13086.
Campbell, P. J., Stephens, P. J., Pleasance, E. D., O'Meara, S., Li, H., Santarius, T., Stebbings, L. A., Leroy, C., Edkins, S., Hardy, C., et al. (2008b). Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat Genet 40, 722-729.
Cecchi, F., Rabe, D. C., and Bottaro, D. P. (2010). Targeting the HGF/Met signalling pathway in cancer. Eur J Cancer 46, 1260-1270.
Chan, J. A., Krichevsky, A. M., and Kosik, K. S. (2005). MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65, 6029-6033.
Chang, T. C., Wentzel, E. A., Kent, O. A., Ramachandran, K., Mullendore, M., Lee, K. H., Feldmann, G., Yamakuchi, M., Ferlito, M., Lowenstein, C. J., et al. (2007). Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26, 745-752.
Chirgadze, D. Y., Hepple, J., Byrd, R. A., Sowdhamini, R., Blundell, T. L., and Gherardi, E. (1998). Insights into the structure of hepatocyte growth factor/scatter factor (HGF/SF) and implications for receptor activation. FEBS Lett 430, 126-129.
Chiyomaru, T., Enokida, H., Tatarano, S., Kawahara, K., Uchida, Y., Nishiyama, K., Fujimura, L., Kikkawa, N., Seki, N., and Nakagawa, M. (2010). miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer 102, 883-891.
Cho, W. C., Chow, A. S., and Au, J. S. (2011). MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1. RNA Biol 8.
Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., Wojcik, S. E., Aqeilan, R. I., Zupo, S., Dono, M., et al. (2005). miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102, 13944-13949.
Comoglio, P. M., Giordano, S., and Trusolino, L. (2008). Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 7, 504-516.
Cooper, C. S., Park, M., Blair, D. G., Tainsky, M. A., Huebner, K., Croce, C. M., and Vande Woude, G. F. (1984). Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311, 29-33.
Corsten, M. F., Miranda, R., Kasmieh, R., Krichevsky, A. M., Weissleder, R., and Shah, K. (2007). MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res 67, 8994-9000.
Craig, V. J., Cogliatti, S. B., Imig, J., Renner, C., Neuenschwander, S., Rehrauer, H., Schlapbach, R., Dirnhofer, S., Tzankov, A., and Muller, A. (2011). Myc-mediated repression of microRNA-34a promotes high grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood.
Deschenes, J., Bourdeau, V., White, J. H., and Mader, S. (2007). Regulation of GREB1 transcription by estrogen receptor alpha through a multipartite enhancer spread over 20 kb of upstream flanking sequences. J Biol Chem 282, 17335-17339.
Ding, J., Huang, S., Wu, S., Zhao, Y., Liang, L., Yan, M., Ge, C., Yao, J., Chen, T., Wan, D., et al. (2010). Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nat Cell Biol 12, 390-399.
Dohner, H., Stilgenbauer, S., Benner, A., Leupolt, E., Krober, A., Bullinger, L., Dohner, K., Bentz, M., and Lichter, P. (2000). Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343, 1910-1916.
Eads, C. A., Danenberg, K. D., Kawakami, K., Saltz, L. B., Danenberg, P. V., and Laird, P. W. (1999). CpG island hypermethylation in human colorectal tumors is not associated with DNAmethyltransferase overexpression. Cancer Res 59, 2302-2306.
El-Serag, H. B., and Rudolph, K. L. (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132, 2557-2576.
Esquela-Kerscher, A., and Slack, F. J. (2006). Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 6, 259-269.
Eyholzer, M., Schmid, S., Wilkens, L., Mueller, B. U., and Pabst, T. (2010). The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML. Br J Cancer 103, 275-284.
Fabbri, M., Garzon, R., Cimmino, A., Liu, Z., Zanesi, N., Callegari, E., Liu, S., Alder, H., Costinean, S., Fernandez-Cymering, C., et al. (2007). MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 104, 15805-15810.
Filipowicz, W., Bhattacharyya, S. N., and Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9, 102-114.
Fisher, B., Dignam, J., Bryant, J., DeCillis, A., Wickerham, D. L., Wolmark, N., Costantino, J., Redmond, C., Fisher, E. R., Bowman, D. M., et al. (1996). Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 88, 1529-1542.
Flynt, A. S., and Lai, E. C. (2008). Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 9, 831-842.
Fornari, F., Gramantieri, L., Ferracin, M., Veronese, A., Sabbioni, S., Calin, G. A., Grazi, G. L., Giovannini, C., Croce, C. M., Bolondi, L., and Negrini, M. (2008). MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 27, 5651-5661.
Forner, A., Hessheimer, A. J., Isabel Real, M., and Bruix, J. (2006). Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol 60, 89-98.
Garofalo, M., Di Leva, G., Romano, G., Nuovo, G., Suh, S. S., Ngankeu, A., Taccioli, C., Pichiorri, F., Alder, H., Secchiero, P., et al. (2009). miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell 16, 498-509.
Garzon, R., Liu, S., Fabbri, M., Liu, Z., Heaphy, C. E., Callegari, E., Schwind, S., Pang, J., Yu, J., Muthusamy, N., et al. (2009). MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113, 6411-6418.
Ghosh, M. G., Thompson, D. A., and Weigel, R. J. (2000). PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer. Cancer Res 60, 6367-6375.
Gramantieri, L., Ferracin, M., Fornari, F., Veronese, A., Sabbioni, S., Liu, C. G., Calin, G. A., Giovannini, C., Ferrazzi, E., Grazi, G. L., et al. (2007). Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res 67, 6092-6099.
Gregersen, L. H., Jacobsen, A. B., Frankel, L. B., Wen, J., Krogh, A., and Lund, A. H. (2010). MicroRNA-145 targets YES and STAT1 in colon cancer cells. PLoS One 5, e8836.
Guo, Y., Chen, Z., Zhang, L., Zhou, F., Shi, S., Feng, X., Li, B., Meng, X., Ma, X., Luo, M., et al. (2008). Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Res 68, 26-33.
Hammond, S. M., Bernstein, E., Beach, D., and Hannon, G. J. (2000). An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404, 293-296.
Hanahan, D., and Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674.
Harvey, J. M., Clark, G. M., Osborne, C. K., and Allred, D. C. (1999). Estrogen receptor status byimmunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17, 1474-1481.
Hayashita, Y., Osada, H., Tatematsu, Y., Yamada, H., Yanagisawa, K., Tomida, S., Yatabe, Y., Kawahara, K., Sekido, Y., and Takahashi, T. (2005). A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65, 9628-9632.
He, L., He, X., Lim, L. P., de Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., et al. (2007). A microRNA component of the p53 tumour suppressor network. Nature 447, 1130-1134.
He, L., Thomson, J. M., Hemann, M. T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S. W., Hannon, G. J., and Hammond, S. M. (2005). A microRNA polycistron as a potential human oncogene. Nature 435, 828-833.
Hou, J., Lin, L., Zhou, W., Wang, Z., Ding, G., Dong, Q., Qin, L., Wu, X., Zheng, Y., Yang, Y., et al. (2011). Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell 19, 232-243.
Iorio, M. V., Ferracin, M., Liu, C. G., Veronese, A., Spizzo, R., Sabbioni, S., Magri, E., Pedriali, M., Fabbri, M., Campiglio, M., et al. (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65, 7065-7070.
Iorio, M. V., Visone, R., Di Leva, G., Donati, V., Petrocca, F., Casalini, P., Taccioli, C., Volinia, S., Liu, C. G., Alder, H., et al. (2007). MicroRNA signatures in human ovarian cancer. Cancer Res 67, 8699-8707.
Jaiyesimi, I. A., Buzdar, A. U., Decker, D. A., and Hortobagyi, G. N. (1995). Use of tamoxifen for breast cancer: twenty-eight years later. J Clin Oncol 13, 513-529.
Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., and Slack, F. J. (2005). RAS is regulated by the let-7 microRNA family. Cell 120, 635-647.
Johnston, R. J., and Hobert, O. (2003). A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426, 845-849.
Jones, P. A., and Laird, P. W. (1999). Cancer epigenetics comes of age. Nat Genet 21, 163-167.
Jopling, C. L., Yi, M., Lancaster, A. M., Lemon, S. M., and Sarnow, P. (2005). Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309, 1577-1581.
Kanai, Y., and Hirohashi, S. (2007). Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis 28, 2434-2442.
Kent, O. A., Chivukula, R. R., Mullendore, M., Wentzel, E. A., Feldmann, G., Lee, K. H., Liu, S., Leach, S. D., Maitra, A., and Mendell, J. T. (2010). Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev 24, 2754-2759.
Ketting, R. F., Fischer, S. E., Bernstein, E., Sijen, T., Hannon, G. J., and Plasterk, R. H. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15, 2654-2659.
Kim, H., Kwon, Y. M., Kim, J. S., Han, J., Shim, Y. M., Park, J., and Kim, D. H. (2006). Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancer. Cancer 107, 1042-1049.
Kim, V. N. (2004). MicroRNA precursors in motion: exportin-5 mediates their nuclear export. Trends Cell Biol 14, 156-159.
Kim, Y. K., and Kim, V. N. (2007). Processing of intronic microRNAs. EMBO J 26, 775-783.
Kondo, N., Toyama, T., Sugiura, H., Fujii, Y., and Yamashita, H. (2008). miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res 68, 5004-5008.
Lawrie, C. H., Soneji, S., Marafioti, T., Cooper, C. D., Palazzo, S., Paterson, J. C., Cattan, H., Enver, T., Mager, R., Boultwood, J., et al. (2007). MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer 121, 1156-1161.
Lecellier, C. H., Dunoyer, P., Arar, K., Lehmann-Che, J., Eyquem, S., Himber, C., Saib, A., and Voinnet, O. (2005). A cellular microRNA mediates antiviral defense in human cells. Science 308, 557-560.
Lee, R. C., Feinbaum, R. L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854.
Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Radmark, O., Kim, S., and Kim, V. N. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415-419.
Lee, Y., Jeon, K., Lee, J. T., Kim, S., and Kim, V. N. (2002). MicroRNA maturation: stepwise processing and subcellular localization. EMBO J 21, 4663-4670.
Lewis, B. P., Burge, C. B., and Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20.
Linsley, P. S., Schelter, J., Burchard, J., Kibukawa, M., Martin, M. M., Bartz, S. R., Johnson, J. M., Cummins, J. M., Raymond, C. K., Dai, H., et al. (2007). Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol 27, 2240-2252.
Liu, C., Kelnar, K., Liu, B., Chen, X., Calhoun-Davis, T., Li, H., Patrawala, L., Yan, H., Jeter, C., Honorio, S., et al. (2011). The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17, 211-215.
Lu, S., and Cullen, B. R. (2004). Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and MicroRNA biogenesis. J Virol 78, 12868-12876.
Ma, L., Teruya-Feldstein, J., and Weinberg, R. A. (2007). Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682-688.
Maillot, G., Lacroix-Triki, M., Pierredon, S., Gratadou, L., Schmidt, S., Benes, V., Roche, H., Dalenc, F., Auboeuf, D., Millevoi, S., and Vagner, S. (2009). Widespread estrogen-dependent repression of micrornas involved in breast tumor cell growth. Cancer Res 69, 8332-8340.
Meng, F., Henson, R., Wehbe-Janek, H., Ghoshal, K., Jacob, S. T., and Patel, T. (2007). MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133, 647-658.
Meng, Z., Fu, X., Chen, X., Zeng, S., Tian, Y., Jove, R., Xu, R., and Huang, W. (2010). miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice. Hepatology 52, 2148-2157.
Michael, M. Z., SM, O. C., van Holst Pellekaan, N. G., Young, G. P., and James, R. J. (2003). Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1, 882-891.
Motoyama, K., Inoue, H., Nakamura, Y., Uetake, H., Sugihara, K., and Mori, M. (2008). Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res 14, 2334-2340.
Mott, J. L., Kobayashi, S., Bronk, S. F., and Gores, G. J. (2007). mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 26, 6133-6140.
Mott, J. L., Kurita, S., Cazanave, S. C., Bronk, S. F., Werneburg, N. W., and Fernandez-Zapico, M. E.(2010). Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB. J Cell Biochem 110, 1155-1164.
Murakami, Y., Yasuda, T., Saigo, K., Urashima, T., Toyoda, H., Okanoue, T., and Shimotohno, K. (2006). Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 25, 2537-2545.
Musgrove, E. A., and Sutherland, R. L. (2009). Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 9, 631-643.
Muss, H. B. (1992). Endocrine therapy for advanced breast cancer: a review. Breast Cancer Res Treat 21, 15-26.
Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science 194, 23-28. O'Donnell, K. A., Wentzel, E. A., Zeller, K. I., Dang, C. V., and Mendell, J. T. (2005). c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839-843.
Ota, A., Tagawa, H., Karnan, S., Tsuzuki, S., Karpas, A., Kira, S., Yoshida, Y., and Seto, M. (2004). Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res 64, 3087-3095.
Ozaki, I., Mizuta, T., Zhao, G., Zhang, H., Yoshimura, T., Kawazoe, S., Eguchi, Y., Yasutake, T., Hisatomi, A., Sakai, T., and Yamamoto, K. (2003). Induction of multiple matrix metalloproteinase genes in human hepatocellular carcinoma by hepatocyte growth factor via a transcription factor Ets-1. Hepatol Res 27, 289-301.
Ozsolak, F., Poling, L. L., Wang, Z., Liu, H., Liu, X. S., Roeder, R. G., Zhang, X., Song, J. S., and Fisher, D. E. (2008). Chromatin structure analyses identify miRNA promoters. Genes Dev 22, 3172-3183.
Park, M., Dean, M., Cooper, C. S., Schmidt, M., O'Brien, S. J., Blair, D. G., and Vande Woude, G. F. (1986). Mechanism of met oncogene activation. Cell 45, 895-904.
Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., Maller, B., Hayward, D. C., Ball, E. E., Degnan, B., Muller, P., et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408, 86-89.
Patra, S. K., Patra, A., Zhao, H., and Dahiya, R. (2002). DNA methyltransferase and demethylase in human prostate cancer. Mol Carcinog 33, 163-171.
Pekarsky, Y., Santanam, U., Cimmino, A., Palamarchuk, A., Efanov, A., Maximov, V., Volinia, S., Alder, H., Liu, C. G., Rassenti, L., et al. (2006). Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res 66, 11590-11593.
Petrocca, F., Visone, R., Onelli, M. R., Shah, M. H., Nicoloso, M. S., de Martino, I., Iliopoulos, D., Pilozzi, E., Liu, C. G., Negrini, M., et al. (2008). E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13, 272-286.
Pineau, P., Volinia, S., McJunkin, K., Marchio, A., Battiston, C., Terris, B., Mazzaferro, V., Lowe, S. W., Croce, C. M., and Dejean, A. (2010). miR-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci U S A 107, 264-269.
Poy, M. N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., Macdonald, P. E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., and Stoffel, M. (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226-230.
Qian, C. N., Guo, X., Cao, B., Kort, E. J., Lee, C. C., Chen, J., Wang, L. M., Mai, W. Y., Min, H. Q., Hong, M. H., et al. (2002). Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma. Cancer Res 62, 589-596.
Rajewsky, N. (2006). microRNA target predictions in animals. Nat Genet 38 Suppl, S8-13.
Raveche, E. S., Salerno, E., Scaglione, B. J., Manohar, V., Abbasi, F., Lin, Y. C., Fredrickson, T., Landgraf, P., Ramachandra, S., Huppi, K., et al. (2007). Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood 109, 5079-5086.
Raver-Shapira, N., Marciano, E., Meiri, E., Spector, Y., Rosenfeld, N., Moskovits, N., Bentwich, Z., and Oren, M. (2007). Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 26, 731-743.
Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., Bettinger, J. C., Rougvie, A. E., Horvitz, H. R., and Ruvkun, G. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901-906.
Roldo, C., Missiaglia, E., Hagan, J. P., Falconi, M., Capelli, P., Bersani, S., Calin, G. A., Volinia, S., Liu, C. G., Scarpa, A., and Croce, C. M. (2006). MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 24, 4677-4684.
Sachdeva, M., and Mo, Y. Y. (2010). MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res 70, 378-387.
Sachdeva, M., Zhu, S., Wu, F., Wu, H., Walia, V., Kumar, S., Elble, R., Watabe, K., and Mo, Y. Y. (2009). p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A 106, 3207-3212.
Schepeler, T., Reinert, J. T., Ostenfeld, M. S., Christensen, L. L., Silahtaroglu, A. N., Dyrskjot, L., Wiuf, C., Sorensen, F. J., Kruhoffer, M., Laurberg, S., et al. (2008). Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res 68, 6416-6424.
Schetter, A. J., Leung, S. Y., Sohn, J. J., Zanetti, K. A., Bowman, E. D., Yanaihara, N., Yuen, S. T., Chan, T. L., Kwong, D. L., Au, G. K., et al. (2008). MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 299, 425-436.
Scott, G. K., Goga, A., Bhaumik, D., Berger, C. E., Sullivan, C. S., and Benz, C. C. (2007). Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 282, 1479-1486.
Seike, M., Goto, A., Okano, T., Bowman, E. D., Schetter, A. J., Horikawa, I., Mathe, E. A., Jen, J., Yang, P., Sugimura, H., et al. (2009). MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci U S A 106, 12085-12090.
Selbach, M., Schwanhausser, B., Thierfelder, N., Fang, Z., Khanin, R., and Rajewsky, N. (2008). Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58-63.
Sherman, M. (2005). Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 25, 143-154.
Si, M. L., Zhu, S., Wu, H., Lu, Z., Wu, F., and Mo, Y. Y. (2007). miR-21-mediated tumor growth. Oncogene 26, 2799-2803.
Simpson, E. R., Misso, M., Hewitt, K. N., Hill, R. A., Boon, W. C., Jones, M. E., Kovacic, A., Zhou, J., and Clyne, C. D. (2005). Estrogen--the good, the bad, and the unexpected. Endocr Rev 26, 322-330. Sipeki, S., Bander, E., Buday, L., Farkas, G., Bacsy, E., Ways, D. K., and Farago, A. (1999).
Phosphatidylinositol 3-kinase contributes to Erk1/Erk2 MAP kinase activation associated with hepatocyte growth factor-induced cell scattering. Cell Signal 11, 885-890.
Sun, J., Nawaz, Z., and Slingerland, J. M. (2007). Long-range activation of GREB1 by estrogen receptor via three distal consensus estrogen-responsive elements in breast cancer cells. Mol Endocrinol21, 2651-2662.
Takamizawa, J., Konishi, H., Yanagisawa, K., Tomida, S., Osada, H., Endoh, H., Harano, T., Yatabe, Y., Nagino, M., Nimura, Y., et al. (2004). Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64, 3753-3756.
Tarasov, V., Jung, P., Verdoodt, B., Lodygin, D., Epanchintsev, A., Menssen, A., Meister, G., and Hermeking, H. (2007). Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6, 1586-1593.
Tavazoie, S. F., Alarcon, C., Oskarsson, T., Padua, D., Wang, Q., Bos, P. D., Gerald, W. L., and Massague, J. (2008). Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451, 147-152.
Tay, Y., Zhang, J., Thomson, A. M., Lim, B., and Rigoutsos, I. (2008). MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455, 1124-1128.
Tazawa, H., Tsuchiya, N., Izumiya, M., and Nakagama, H. (2007). Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A 104, 15472-15477.
Thum, T., Catalucci, D., and Bauersachs, J. (2008). MicroRNAs: novel regulators in cardiac development and disease. Cardiovasc Res 79, 562-570.
Trusolino, L., Bertotti, A., and Comoglio, P. M. (2010). MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 11, 834-848.
Tulasne, D., and Foveau, B. (2008). The shadow of death on the MET tyrosine kinase receptor. Cell Death Differ 15, 427-434.
Vargo-Gogola, T., and Rosen, J. M. (2007). Modelling breast cancer: one size does not fit all. Nat Rev Cancer 7, 659-672.
Varnholt, H. (2008). The role of microRNAs in primary liver cancer. Ann Hepatol 7, 104-113.
Wang, S., Bian, C., Yang, Z., Bo, Y., Li, J., Zeng, L., Zhou, H., and Zhao, R. C. (2009). miR-145 inhibits breast cancer cell growth through RTKN. Int J Oncol 34, 1461-1466.
Whittaker, S., Marais, R., and Zhu, A. X. (2010). The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 29, 4989-5005.
Wojta, J., Kaun, C., Breuss, J. M., Koshelnick, Y., Beckmann, R., Hattey, E., Mildner, M., Weninger, W., Nakamura, T., Tschachler, E., and Binder, B. R. (1999). Hepatocyte growth factor increases expression of vascular endothelial growth factor and plasminogen activator inhibitor-1 in human keratinocytes and the vascular endothelial growth factor receptor flk-1 in human endothelial cells. Lab Invest 79, 427-438.
Xie, X., Lu, J., Kulbokas, E. J., Golub, T. R., Mootha, V., Lindblad-Toh, K., Lander, E. S., and Kellis, M. (2005). Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals. Nature 434, 338-345.
Xiong, Y., Fang, J. H., Yun, J. P., Yang, J., Zhang, Y., Jia, W. H., and Zhuang, S. M. (2010). Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology 51, 836-845.
Xu, P., Vernooy, S. Y., Guo, M., and Hay, B. A. (2003). The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol 13, 790-795.
You, W. K., and McDonald, D. M. (2008). The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Rep 41, 833-839.
Yu, F., Yao, H., Zhu, P., Zhang, X., Pan, Q., Gong, C., Huang, Y., Hu, X., Su, F., Lieberman, J., and
Song, E. (2007). let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131, 1109-1123.
Zeng, Y., and Cullen, B. R. (2004). Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res 32, 4776-4785.
Zeng, Y., Yi, R., and Cullen, B. R. (2005). Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J 24, 138-148.
Zhao, J. J., Lin, J., Lwin, T., Yang, H., Guo, J., Kong, W., Dessureault, S., Moscinski, L. C., Rezania, D., Dalton, W. S., et al. (2010). microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood 115, 2630-2639.
Zhu, S., Si, M. L., Wu, H., and Mo, Y. Y. (2007). MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282, 14328-14336.