miR-138-5p contributes to cell proliferation and invasion by targeting Survivin in bladder cancer cells.
miR-138-5p contributes to cell proliferation and invasion by targeting Survivin in bladder cancer cells.
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miR-138-5p 通过靶向膀胱癌细胞中的生存素来促进细胞增殖和侵袭。
DOI：
10.1186/s12943-016-0569-4
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发表时间：
2016-12-15
期刊：
影响因子：
37.3
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Yang R;Liu M;Liang H;Guo S;Guo X;Yuan M;Lian H;Yan X;Zhang S;Chen X;Fang F;Guo H;Zhang C
Survivin（由BIRC 5基因编码）在膀胱癌的发生中起重要作用。在膀胱癌的背景下识别靶向Survivin的miRNA将有助于开发基于Survivin的膀胱癌治疗方法。检测12例膀胱癌组织中miR-138- 5 p和Survivin蛋白的表达水平。通过评估Survivin在过表达或敲低miR-138 - 5 p的人膀胱癌细胞系中的表达，进一步检查miR-138 - 5 p和Survivin之间的相关性。进行荧光素酶报告基因测定以测试miR-138- 5 p与靶基因BIRC 5的直接结合。我们还研究了靶向Survivin的miR-138- 5 p在体内和体外膀胱癌细胞系中的生物学作用。在这项研究中，我们发现Survivin蛋白在正常邻近组织中不存在或弱表达，并在膀胱癌组织中持续上调;然而，mRNA水平变化不大，表明涉及转录后机制。由于microRNA是基因表达的强大转录后调节因子，我们使用生物信息学分析来寻找可能在膀胱癌背景下靶向BIRC 5的microRNA。我们在BIRC 5的3′非翻译区（3′-UTR）中发现了miR-138- 5 p的2个特异性靶向位点。我们进一步鉴定了膀胱癌组织样品中miR-138- 5 p和Survivin蛋白水平之间的负相关性。通过在膀胱癌细胞中过表达或敲低miR-138- 5 p，我们实验证实miR-138- 5 p直接识别BIRC 5转录物的3′-UTR并调节Survivin表达。此外，通过细胞增殖和侵袭测定在体外和使用小鼠异种移植肿瘤模型在体内检查miR-138- 5 p靶向BIRC 5的生物学后果。我们证明了miR-138- 5 p对BIRC 5的抑制抑制了膀胱癌细胞的增殖和侵袭特征，并且miR-138- 5 p通过在异种移植小鼠模型中负调节BIRC 5而发挥抗肿瘤作用。总之，我们的发现提供了关于miR-138- 5 p通过抑制BIRC 5翻译在膀胱癌中作为肿瘤抑制因子的作用的第一条线索。本文的在线版本（doi：10.1186/s12943-016-0569-4）包含补充材料，可供授权用户使用。
Survivin (encoded by the gene BIRC5) plays an important role in the carcinogenesis of bladder cancer. Identifying miRNAs that target Survivin in the setting of bladder cancer will help to develop Survivin-based therapies for bladder cancer. The expression levels of miR-138-5p and Survivin protein were measured in 12 resected bladder cancer specimens. The correlation between miR-138-5p and Survivin was further examined by evaluating Survivin expression in human bladder cancer cell lines that either overexpressed or knocked down miR-138-5p. A luciferase reporter assay was performed to test the direct binding of miR-138-5p to the target gene BIRC5. We also investigated the biological role of miR-138-5p targeting to Survivin in bladder cancer cell lines both in vivo and in vitro. In this study, we found that the Survivin protein was either absent or weakly expressed in normal adjacent tissues and consistently up-regulated in bladder cancer tissues; however, the mRNA levels did not vary as much, suggesting that a post-transcriptional mechanism was involved. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for microRNAs that could potentially target BIRC5 in the setting of bladder cancer. We identified 2 specific targeting sites for miR-138-5p in the 3′ untranslated region (3′-UTR) of BIRC5. We further identified an inverse correlation between miR-138-5p and Survivin protein levels in bladder cancer tissue samples. By overexpressing or knocking down miR-138-5p in bladder cancer cells, we experimentally confirmed that miR-138-5p directly recognizes the 3′-UTR of the BIRC5 transcript and regulates Survivin expression. Furthermore, the biological consequences of the targeting of BIRC5 by miR-138-5p were examined in vitro via cell proliferation and invasion assays and in vivo using a mouse xenograft tumor model. We demonstrated that BIRC5 repression by miR-138-5p suppressed the proliferative and invasive characteristics of bladder cancer cells and that miR-138-5p exerted an anti-tumor effect by negatively regulating BIRC5 in a xenograft mouse model. Taken together, our findings provide the first clues regarding the role of miR-138-5p as a tumor suppressor in bladder cancer by inhibiting BIRC5 translation. The online version of this article (doi:10.1186/s12943-016-0569-4) contains supplementary material, which is available to authorized users.
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DOI：
10.4103/0971-5916.159250
发表时间：
2015-04
期刊：
The Indian journal of medical research
影响因子：
--
作者：
Jaiswal PK;Goel A;Mittal RD
通讯作者：
Mittal RD
影响因子：
3.4
作者：
Breyer, Johannes;Gierth, Michael;Otto, Wolfgang
通讯作者：
Otto, Wolfgang
影响因子：
3.1
作者：
Liang, Jiaqian;Zhang, Yajing;Zhao, Jun
通讯作者：
Zhao, Jun
影响因子：
4.5
作者：
Lee, Eun Joo;Baek, Myungwon;Schmittgen, Thomas D.
通讯作者：
Schmittgen, Thomas D.
影响因子：
11.5
作者：
Shariat, Shahrokh F.;Karakiewicz, Pierre I.;Lotan, Yair
通讯作者：
Lotan, Yair