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微小RNA-6852通过靶向胃癌中的叉头框J1抑制细胞增殖和侵袭。

MicroRNA-6852 suppresses cell proliferation and invasion via targeting forkhead box J1 in gastric cancer.

作者信息

Yu Hui, Zhang Jing, Wen Qu, Dai Yi, Zhang Wanli, Li Fen, Li Juan

机构信息

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

出版信息

Exp Ther Med. 2018 Oct;16(4):3249-3255. doi: 10.3892/etm.2018.6569. Epub 2018 Aug 2.

Abstract

Accumulating evidence suggests that microRNAs (miRs) exert vital functions in the development and progression of multiple types of human cancer. However, the role of miR-6852 in gastric cancer (GC) remains unclear. In the present study, miR-6852 expression was significantly downregulated in GC tissues compared with adjacent normal tissues determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Furthermore, miR-6852 expression levels in patients with GC were reversely correlated with tumor metastasis and TNM stage. Through Cell Counting kit-8 and Transwell assays, it was demonstrated that overexpression of miR-6852 significantly inhibited the proliferation, migration and invasion of GC cells. With regards to the mechanism involved, luciferase reporter assays suggested that miR-6852 directly target forkhead box J1 (FOXJ1) in GC cells. Furthermore, overexpression of miR-6852 markedly inhibited the mRNA and protein expression levels of FOXJ1 in GC cells determined by RT-qPCR and western blot analysis. Additionally, FOXJ1 was overexpressed in GC tissues and cell lines, and its expression was negatively correlated with that of miR-6852 in GC tissues. Rescue assays indicated that overexpression of FOXJ1 significantly reversed the effects of miR-6852 transfection on GC cell proliferation, migration and invasion. Taken together, the present findings demonstrated that miR-6852 exerted a tumor suppressive role through targeting FOXJ1 in GC. These results implied that miR-6852 may be a novel therapeutic target of GC treatment.

摘要

越来越多的证据表明,微小RNA(miR)在多种人类癌症的发生和发展中发挥着重要作用。然而,miR-6852在胃癌(GC)中的作用仍不清楚。在本研究中,通过逆转录定量聚合酶链反应(RT-qPCR)分析确定,与相邻正常组织相比,GC组织中miR-6852的表达显著下调。此外,GC患者的miR-6852表达水平与肿瘤转移和TNM分期呈负相关。通过细胞计数试剂盒-8和Transwell实验表明,miR-6852的过表达显著抑制了GC细胞的增殖、迁移和侵袭。关于其涉及的机制,荧光素酶报告基因实验表明,miR-6852在GC细胞中直接靶向叉头框J1(FOXJ1)。此外,通过RT-qPCR和蛋白质印迹分析确定,miR-6852的过表达显著抑制了GC细胞中FOXJ1的mRNA和蛋白质表达水平。此外,FOXJ1在GC组织和细胞系中过表达,其在GC组织中的表达与miR-6852呈负相关。挽救实验表明,FOXJ1的过表达显著逆转了miR-6852转染对GC细胞增殖、迁移和侵袭的影响。综上所述,本研究结果表明,miR-6852在GC中通过靶向FOXJ1发挥肿瘤抑制作用。这些结果表明,miR-6852可能是GC治疗的一个新的治疗靶点。

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