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miR-342-3p 通过 miR-377/E2F1 信号通路抑制神经胶质瘤细胞增殖。

Glioma cell proliferation is inhibited by miR-342-3p, miR-377 / E2F1 signaling pathway.

机构信息

The Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.

出版信息

Neoplasma. 2019 Jul 23;66(4):524-531. doi: 10.4149/neo_2018_180805N574.

Abstract

Recent years, micoRNAs (miRNAs) have been reported to be critical regulators to influence tumor genesis or further progression by directly targeting downstream tumor related genes in glioma. However, there're still many underlying mechanisms related to miRNAs signaling pathway remain to be uncovered in glioma. In the present study, we found that miR-342-3p and miR-377 inhibited the glioma cell line proliferation and arrested the cell cycle at G1 phase. Inhibition of the function of miR-342-3p and miR-377 promoted the cell proliferation. miR-342-3p and miR-377 target the E2F1 3'UTR to repress its expression on both mRNA and protein level. Downregulation of E2F1 inhibited the cell proliferation and arrested the cell cycle. Overexpression of E2F1 blocked the proliferation repression caused by miR-342-3p or miR-377 in glioma cells. This study showed the function of miR-342-3p, miR-377/E2F1 axis in regulating glioma cells proliferation and provided the potential therapeutic target.

摘要

近年来,研究表明 microRNAs(miRNAs)通过直接靶向胶质瘤下游肿瘤相关基因,成为影响肿瘤发生或进一步进展的关键调节因子。然而,miRNAs 信号通路相关的许多潜在机制仍有待在胶质瘤中发现。在本研究中,我们发现 miR-342-3p 和 miR-377 抑制了神经胶质瘤细胞系的增殖,并将细胞周期阻滞在 G1 期。抑制 miR-342-3p 和 miR-377 的功能促进了细胞增殖。miR-342-3p 和 miR-377 靶向 E2F1 的 3'UTR,在 mRNA 和蛋白水平上抑制其表达。E2F1 的下调抑制了细胞增殖并将细胞周期阻滞在 G1 期。E2F1 的过表达阻断了 miR-342-3p 或 miR-377 在神经胶质瘤细胞中引起的增殖抑制。本研究表明了 miR-342-3p、miR-377/E2F1 轴在调节神经胶质瘤细胞增殖中的作用,并为潜在的治疗靶点提供了依据。

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