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微小RNA-132通过阻断泛素特异性蛋白酶9X诱导的上皮-间质转化来抑制肺癌细胞的迁移和侵袭。

miR-132 suppresses the migration and invasion of lung cancer cells by blocking USP9X-induced epithelial-mesenchymal transition.

作者信息

Guo Huihui, Zhang Xilin, Chen Qiuqiang, Bao Ying, Dong Chaohui, Wang Xiang

机构信息

Key Laboratory for Translational Medicine, First Affiliated Hospital, Huzhou UniversityHuzhou 313000, Zhejiang, China.

出版信息

Am J Transl Res. 2018 Jan 15;10(1):224-234. eCollection 2018.

Abstract

miR-132, a microRNA, has been reported to be down-regulated in several human cancers and is related with tumor progression; however, its function in non-small cell lung cancer (NSCLC) progression remains unclear. This study aimed to investigate the putative role of miR-132 in the metastasis of NSCLC. We determined the function of miR-132 in the migration and invasion of a NSCLC cell line using a miR-132 inhibitor and mimic. Our results showed overexpression of miR-132 significantly inhibited the migration and invasion of NSCLC cells . We then identified USP9X as a potential target of miR-132, and demonstrated miR-132 could regulate the expression of USP9X at both the mRNA and protein level. miR-132 could directly bind to the 3' untranslated region (3'-UTR) of USP9X. Inhibition of USP9X by its inhibitor WP1130 reduced the migration and invasion of NSCLC cells. Furthermore, USP9X inhibition also reversed the increased migration and invasion mediated by miR-132 inhibition. We found USP9X inhibition up-regulated expression of the epithelial-mesenchymal transition (EMT) marker E-cadherin, but down-regulated vimentin expression. A similar effect was seen with miR-132 overexpression, while the opposite effect occurred with miR-132 knockdown. USP9X inhibition reversed the miR-132 inhibitor-induced vimentin up-regulation and E-cadherin down-regulation. Taken together, these results indicate miR-132 prohibits the migration and invasion of NSCLC cells via targeting USP9X-induced EMT. Our data provides further evidence for the critical role of miR-132 and USP9X in regulating cell invasion and migration of NSCLC.

摘要

微小RNA miR-132已被报道在多种人类癌症中表达下调,并与肿瘤进展相关;然而,其在非小细胞肺癌(NSCLC)进展中的作用仍不清楚。本研究旨在探讨miR-132在NSCLC转移中的假定作用。我们使用miR-132抑制剂和模拟物确定了miR-132在NSCLC细胞系迁移和侵袭中的功能。我们的结果表明,miR-132的过表达显著抑制了NSCLC细胞的迁移和侵袭。然后,我们确定泛素特异性蛋白酶9X(USP9X)是miR-132的潜在靶点,并证明miR-132可以在mRNA和蛋白质水平上调节USP9X的表达。miR-132可以直接与USP9X的3'非翻译区(3'-UTR)结合。其抑制剂WP1130对USP9X的抑制作用降低了NSCLC细胞的迁移和侵袭。此外,USP9X抑制还逆转了miR-132抑制介导的迁移和侵袭增加。我们发现USP9X抑制上调了上皮-间质转化(EMT)标志物E-钙黏蛋白的表达,但下调了波形蛋白的表达。miR-132过表达也有类似效果,而miR-132敲低则产生相反效果。USP9X抑制逆转了miR-132抑制剂诱导的波形蛋白上调和E-钙黏蛋白下调。综上所述,这些结果表明miR-132通过靶向USP9X诱导的EMT来抑制NSCLC细胞的迁移和侵袭。我们的数据为miR-132和USP9X在调节NSCLC细胞侵袭和迁移中的关键作用提供了进一步证据。

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