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微小RNA-409-3p通过靶向高迁移率族核小体结合域5抑制胶质瘤细胞的侵袭和增殖。

MicroRNA-409-3p Represses Glioma Cell Invasion and Proliferation by Targeting High-Mobility Group Nucleosome-Binding Domain 5.

作者信息

Cao Yidong, Zhang Liang, Wei Minghao, Jiang Xue, Jia Dong

出版信息

Oncol Res. 2017 Aug 7;25(7):1097-1107. doi: 10.3727/096504017X14836170586829. Epub 2017 Jan 20.

Abstract

Emerging evidence has suggested that aberrantly expressed microRNAs (miRNAs) are associated with glioma development and progression. The aberrant expression of miR-409-3p has been reported in several human cancers. However, little is known about the function of miR-409-3p in gliomas. The aim of this study was to investigate the specific role and molecular mechanism of miR-409-3p in gliomas. In the present study, we found that miR-409-3p was downregulated in glioma tissue and cell lines. Overexpression of miR-409-3p inhibited glioma cell invasion and proliferation, whereas suppression of miR-409-3p promoted glioma cell invasion and proliferation. High-mobility group nucleosome-binding domain 5 (HMGN5), a well-known oncogene in gliomas, was identified as a functional target of miR-409-3p using bioinformatics, dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. Furthermore, miR-409-3p was found to regulate the expression of matrix metalloproteinase 2 and cyclin D1. Restoration of HMGN5 expression significantly reversed the inhibitory effects of miR-409-3p overexpression on glioma cell invasion and proliferation. Taken together, our results suggest that miR-409-3p inhibits glioma cell invasion and proliferation by targeting HMGN5, representing a potential therapeutic target for glioma.

摘要

新出现的证据表明,异常表达的微小RNA(miRNA)与胶质瘤的发生和发展有关。miR-409-3p的异常表达已在几种人类癌症中被报道。然而,关于miR-409-3p在胶质瘤中的功能知之甚少。本研究的目的是探讨miR-409-3p在胶质瘤中的具体作用和分子机制。在本研究中,我们发现miR-409-3p在胶质瘤组织和细胞系中表达下调。miR-409-3p的过表达抑制了胶质瘤细胞的侵袭和增殖,而抑制miR-409-3p则促进了胶质瘤细胞的侵袭和增殖。高迁移率族核小体结合域5(HMGN5)是胶质瘤中一种著名的癌基因,通过生物信息学、双荧光素酶报告基因检测、实时定量聚合酶链反应和蛋白质免疫印迹分析,被确定为miR-409-3p的功能靶点。此外,发现miR-409-3p可调节基质金属蛋白酶2和细胞周期蛋白D1的表达。恢复HMGN5的表达显著逆转了miR-409-3p过表达对胶质瘤细胞侵袭和增殖的抑制作用。综上所述,我们的结果表明,miR-409-3p通过靶向HMGN5抑制胶质瘤细胞的侵袭和增殖,这代表了胶质瘤的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/7841248/6e23d0f52e86/OR-25-1097-g001.jpg

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