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微小RNA-331通过靶向星形胶质细胞上调基因-1抑制黑色素瘤细胞的增殖和侵袭。

MicroRNA-331 Inhibits Proliferation and Invasion of Melanoma Cells by Targeting Astrocyte-Elevated Gene-1.

作者信息

Chen Li, Ma Guozhang, Cao Xiaohui, An Xiaoxia, Liu Xiguang

机构信息

Department of Dermatology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, P.R. China.

出版信息

Oncol Res. 2018 Oct 17;26(9):1429-1437. doi: 10.3727/096504018X15186047251584. Epub 2018 Feb 17.

Abstract

Melanoma is characterized by aggressive invasion, early metastasis, and resistance to existing chemotherapeutic agents. Accumulated studies have reported that microRNA (miRNA) is a potentially robust molecular tool for developing future therapeutic technologies. Therefore, examining the expression patterns, biological roles, and associated mechanisms of cancer-related miRNAs in melanoma is essential for developing novel therapeutic targets for patients with this disease. In this study, miRNA-331 (miR-331) was underexpressed in melanoma tissues and cell lines. Functional assays revealed that the enforced expression of miR-331 inhibited cell proliferation and invasion. In addition, astrocyte-elevated gene-1 (AEG-1) was identified as a novel target of miR-331 through bioinformatics analysis, reverse transcription quantitative polymerase chain reaction analysis, Western blot analysis, dual-luciferase reporter assay, and Spearman's correlation analysis. Furthermore, reintroduction of AEG-1 partially abrogated the inhibitory effects of miR-331 overexpression on the proliferation and invasion of melanoma cells. Moreover, miR-331 suppressed the activation of the PTEN/AKT signaling pathway in melanoma by inhibiting AEG-1. In short, miR-331 may play tumor-suppressive roles in melanoma by directly targeting AEG-1 and regulating the PTEN/AKT signaling pathway, suggesting that miR-331 could be investigated as a therapeutic strategy for patients with this malignancy.

摘要

黑色素瘤的特点是侵袭性强、早期转移且对现有化疗药物耐药。越来越多的研究报道,微小RNA(miRNA)是开发未来治疗技术的一种潜在有力分子工具。因此,研究黑色素瘤中与癌症相关的miRNA的表达模式、生物学作用及相关机制,对于为该疾病患者开发新的治疗靶点至关重要。在本研究中,miRNA - 331(miR - 331)在黑色素瘤组织和细胞系中表达下调。功能分析表明,miR - 331的强制表达抑制细胞增殖和侵袭。此外,通过生物信息学分析、逆转录定量聚合酶链反应分析、蛋白质免疫印迹分析、双荧光素酶报告基因检测和Spearman相关性分析,星形胶质细胞上调基因1(AEG - 1)被确定为miR - 331的一个新靶点。此外,重新引入AEG - 1部分消除了miR - 331过表达对黑色素瘤细胞增殖和侵袭的抑制作用。此外,miR - 331通过抑制AEG - 1抑制黑色素瘤中PTEN/AKT信号通路的激活。简而言之,miR - 331可能通过直接靶向AEG - 1并调节PTEN/AKT信号通路在黑色素瘤中发挥肿瘤抑制作用,这表明miR - 331可作为该恶性肿瘤患者的一种治疗策略进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47e/7844642/70f9b202f52a/OR-26-1429-g001.jpg

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