MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3
MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3
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MicroRNA-125b 通过靶向 E2F3 抑制膀胱癌的发展
DOI：
10.1002/ijc.25509
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发表时间：
2011-04-15
影响因子：
6.4
通讯作者：
Lin, Tianxin
中科院分区：
文献类型：
--
作者：
Huang, Li;Luo, Junhua;Lin, Tianxin
越来越多的证据表明，某些microRNA（miRNAs）的失调可能有助于肿瘤的发生。microRNA-125 b（miR-125 b）与细胞增殖和分化密切相关，在多种肿瘤中表达下调。然而，miR-125 b在膀胱肿瘤发生中的生物学功能仍然未知。在我们的研究中，我们发现miR-125 b在膀胱癌组织和四种膀胱癌细胞系中的表达显著降低。此外，miR-125 b在体外可抑制膀胱癌细胞的集落形成和裸鼠体内成瘤。E2 F3是miR-125 b的靶基因，在大多数低分化膀胱癌中过表达，是G1/ S转换的关键基因。在膀胱癌组织和细胞系中检测到E2 F3 mRNA和蛋白表达水平，有趣的是，在膀胱癌组织和4种E2 F3非扩增细胞系中发现miR-125 b和E2 F3蛋白水平呈负相关。miR-125 b的导入可降低E2 F3蛋白的表达，但对E2 F3 mRNA的表达无影响。此外，我们观察到转染miR-125 b可以抑制Cyclin A2的表达，Cyclin A2是参与G1/ S转换的E2 Fs应答基因之一。这些结果表明miR-125 b可能通过E2 F3-Cyclin A2信号通路调控G1/ S转换。总之，miR-125 b可能在膀胱尿路上皮中起肿瘤抑制剂的作用，并且miR-125 b的下调可能有助于膀胱癌的肿瘤发生。
Increasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to tumorigenesis. microRNA- 125b (miR-125b) was implicated to have close relationship with cell proliferation and differentiation, and downregulation of miR-125b was observed in various types of cancers. However, the biological function of miR-125b in bladder tumorigenesis is still unknown. In our study, we showed that the expression of miR-125b was significantly decreased in bladder cancer tissues and four bladder cancer cell lines. Moreover, miR-125b could suppress bladder cancer cells to form colonies in vitro and to develop tumors in nude mice. E2F3, which was critical for G1/ S transition and was overexpressed in most of poor-differentiated bladder cancers, was identified as a target of miR-125b by luciferase assay. The E2F3 mRNA and protein expression levels were detected in bladder cancer tissues and cell lines, and interestingly, inverse correlations between miR-125b and E2F3 protein level were found in bladder cancer tissues and four E2F3 nonamplified cell lines. Introduction of miR-125b could reduce the expression of E2F3 protein but not the E2F3 mRNA. In addition, we observed that transfection of miR-125b could inhibit the expression of Cyclin A2, one of the E2Fs-responsive genes involved in G1/ S transition. These results suggest that miR-125b may regulate G1/ S transition through the E2F3-Cyclin A2 signaling pathway. Taken together, miR-125b may act as a tumor suppressor in bladder urothelium, and downregulation of miR-125b may contribute to the tumorigenesis of bladder cancer.