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miR-485-3p的下调通过靶向RNF135促进胶质母细胞瘤细胞的增殖和迁移。

Downregulation of miR-485-3p promotes glioblastoma cell proliferation and migration via targeting RNF135.

作者信息

Zhang Ye, Sui Rui, Chen Yi, Liang Haiyang, Shi Ji, Piao Haozhe

机构信息

Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.

出版信息

Exp Ther Med. 2019 Jul;18(1):475-482. doi: 10.3892/etm.2019.7600. Epub 2019 May 23.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that serve pivotal roles in human diseases. Several miRNAs, such as miR-485-3p, have been identified as potential biomarkers for predicting overall survival of patients with glioblastoma (GBM). However, the underlying mechanism of miRNAs in promoting GBM progression remains unknown. In the present study, decreased miR-485-3p expression was detected in tumor tissues from patients with GBM. Using western blot analysis, reverse transcription-quantitative PCR and dual luciferase reporter assay, ring finger protein 135 (RNF135) was confirmed as a target gene of miR-485-3p in GBM cells. Through silencing of RNF135, miR-485-3p inactivated the mitogen-activated protein kinase/ERK1/2 pathway in GBM cells. Moreover, functional assays demonstrated that miR-485-3p inhibited GBM cell proliferation and migration whilst overexpression of RNF135 reversed this effect. Additionally, a negative correlation between miR-485-3p and RNF135 mRNA expression was observed in tissues from patients with glioblastoma. In conclusion, the present results demonstrated that miR-485-3p functioned as a tumor suppressor which suggested that miR-485-3p might have a role in GBM progression.

摘要

微小RNA(miRNA)是一类小的非编码RNA,在人类疾病中发挥着关键作用。几种miRNA,如miR-485-3p,已被确定为预测胶质母细胞瘤(GBM)患者总生存期的潜在生物标志物。然而,miRNA促进GBM进展的潜在机制仍不清楚。在本研究中,检测到GBM患者肿瘤组织中miR-485-3p表达降低。通过蛋白质免疫印迹分析、逆转录定量PCR和双荧光素酶报告基因检测,证实环指蛋白135(RNF135)是GBM细胞中miR-485-3p的靶基因。通过沉默RNF135,miR-485-3p使GBM细胞中的丝裂原活化蛋白激酶/ERK1/2信号通路失活。此外,功能分析表明,miR-485-3p抑制GBM细胞增殖和迁移,而RNF135的过表达则逆转了这种作用。此外,在胶质母细胞瘤患者的组织中观察到miR-485-3p与RNF135 mRNA表达呈负相关。总之,本研究结果表明miR-485-3p发挥肿瘤抑制作用,提示其可能在GBM进展中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11a6/6566029/3844451f1954/etm-18-01-0475-g00.jpg

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