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

波形蛋白 上皮-间质转换 基因敲除 癌症研究 小RNA 细胞迁移 转移 肺癌 体外 生物 细胞培养 化学 癌症 医学 病理 免疫学 基因 免疫组织化学 生物化学 遗传学
作者
Huihui Guo,Xilin Zhang,Qiuqiang Chen,Ying Bao,Chaohui Dong,Xiang Wang
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期刊:PubMed 卷期号:10 (1): 224-234 被引量:9
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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 in vitro using a miR-132 inhibitor and mimic. Our results showed overexpression of miR-132 significantly inhibited the migration and invasion of NSCLC cells in vitro. 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.

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