【作者】 谭胜；

【导师】 朱涛；

【作者基本信息】 中国科学技术大学 ， 细胞生物学， 2011， 博士

【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。更多还原

【Abstract】 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.更多还原