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微小RNA-30a-5p通过靶向抑制高侵袭性非小细胞肺癌细胞系中的丝切蛋白-2来抑制上皮-间质转化。

MicroRNA-30a-5p suppresses epithelial-mesenchymal transition by targeting profilin-2 in high invasive non-small cell lung cancer cell lines.

作者信息

Yan Jiliang, Ma Chunyan, Gao Yue

机构信息

Department of Clinical Laboratory, Kaifeng Central Hospital, Kaifeng, Henan 475000, P.R. China.

Department of Clinical Laboratory, Beibei Traditional Chinese Medical Hospital, Chongqing 400700, P.R. China.

出版信息

Oncol Rep. 2017 May;37(5):3146-3154. doi: 10.3892/or.2017.5566. Epub 2017 Apr 11.

Abstract

PFN2 is an invasion promoter in several cancers including lung cancer. However, the probable effects and underlying mechanisms of PFN2 in tumor cell epithelial-mesenchymal-transition (EMT) of non-small cell lung cancer (NSCLC) remain poorly understood. The protein and mRNA levels of PFN2 in human bronchial epithelial cell line 16HBE and three NSCLC cell lines A549, NCI-H520 and 95D were assessed. The gain-of-function (overexpression) and loss‑of-function (siRNA) experiments of PFN2 were performed in 95D cells. A dual-luciferase reporter assay, western blotting and real-time PCR were used to investigate the relationship between PFN2 and miR‑30a‑5p. PFN2 was upregulated in three NSCLC cell lines, and the highest in 95D cell line. Furthermore, the upregulation of PFN2 promoted, whereas the downregulation of PFN2 suppressed invasion and EMT in 95D. Dual-luciferase reporter assay showed that miR‑30a‑5p directly interacts with the 3'-untranslated region (3'-UTR) of PFN2 mRNA. Interestingly, miR‑30a‑5p negatively regulates the expression of PFN2 and suppresses EMT and invasion in 95D. In summary, the present study demonstrated that miR‑30a‑5p inhibits EMT and invasion in high invasive NSCLC cell lines via targeting PFN2. Suggesting the association of miR‑30a‑5p and PFN2 may play an essential role in the development of NSCLC by modulating EMT and cell invasion.

摘要

PFN2是包括肺癌在内的多种癌症中的侵袭促进因子。然而,PFN2在非小细胞肺癌(NSCLC)肿瘤细胞上皮-间质转化(EMT)中的可能作用及潜在机制仍知之甚少。评估了人支气管上皮细胞系16HBE和三种NSCLC细胞系A549、NCI-H520和95D中PFN2的蛋白质和mRNA水平。在95D细胞中进行了PFN2的功能获得(过表达)和功能丧失(siRNA)实验。采用双荧光素酶报告基因检测、蛋白质印迹法和实时定量PCR研究PFN2与miR-30a-5p之间的关系。PFN2在三种NSCLC细胞系中上调,在95D细胞系中最高。此外,PFN2的上调促进了95D细胞的侵袭和EMT,而PFN2的下调则抑制了侵袭和EMT。双荧光素酶报告基因检测表明,miR-30a-5p直接与PFN2 mRNA的3'-非翻译区(3'-UTR)相互作用。有趣的是,miR-30a-5p负向调节PFN2的表达,并抑制95D细胞的EMT和侵袭。总之,本研究表明,miR-30a-5p通过靶向PFN2抑制高侵袭性NSCLC细胞系中的EMT和侵袭。提示miR-30a-5p与PFN2的关联可能通过调节EMT和细胞侵袭在NSCLC的发生发展中起重要作用。

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