miRNA在调控恶性肿瘤细胞的恶性进展中的作用研究

被引:0
作者
谭胜
机构
[1] 中国科学技术大学
关键词
miRNA; 恶性肿瘤; 肝癌; 乳腺癌; 迁移; 侵袭; 增殖; c-MET基因; GREB1基因;
D O I
暂无
年度学位
2011
学位类型
博士
导师
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。
引用
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页数:93
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