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microRNA-138 通过靶向 Sirt1 抑制肝癌细胞增殖。

MicroRNA-138 inhibits cell proliferation in hepatocellular carcinoma by targeting Sirt1.

机构信息

Department of Hepatobiliary Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China.

出版信息

Oncol Rep. 2017 Aug;38(2):1067-1074. doi: 10.3892/or.2017.5782. Epub 2017 Jul 3.

Abstract

MicroRNAs (miRNAs) are a family of small, non‑coding RNA molecules that are highly conserved across species and function as regulators of gene expression. In the present study, we revealed that miR-138 expression was at a low level while sirtuin type 1 (Sirt1) mRNA expression was at high level in hepatocellular carcinoma tissues and cell lines by using real-time PCR and western blot assays, and the functions of miR-138 were achieved via targeting of Sirt1 using luciferase reporter gene vector and RNA immunoprecipitation assays. Overexpression of miR-138 attenuated Sirt1 expression and inhibited cell proliferation by using CCK-8 and BrdU assays. The inhibitory effect of miR-138 could be partially restored by forced expression of Sirt1 in cells. Our data revealed a crucial role and mechanism of miR-138 in the regulation of hepatocellular carcinoma cell growth via the miR-138/Sirt1 axis, and miR-138 could be an important potential target for the clinical management of hepatocellular carcinoma in the future.

摘要

微小 RNA(miRNAs)是一类高度保守的小非编码 RNA 分子,作为基因表达的调节剂发挥作用。在本研究中,我们通过实时 PCR 和 Western blot 检测发现,miR-138 在肝癌组织和细胞系中的表达水平较低,而 Sirtuin 类型 1(Sirt1)mRNA 的表达水平较高,通过使用荧光素酶报告基因载体和 RNA 免疫沉淀检测发现,miR-138 通过靶向 Sirt1 发挥作用。使用 CCK-8 和 BrdU 检测发现,miR-138 的过表达减弱了 Sirt1 的表达并抑制了细胞增殖。在细胞中强制表达 Sirt1 可以部分恢复 miR-138 的抑制作用。我们的数据揭示了 miR-138 通过 miR-138/Sirt1 轴在调节肝癌细胞生长中的重要作用和机制,miR-138 可能成为未来肝癌临床管理的一个重要潜在靶点。

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