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微小 RNA-363-3p 通过靶向 HMGA2 抑制肝癌发生,并且与肝癌分期相关。

MicroRNA‑363‑3p inhibits hepatocarcinogenesis by targeting HMGA2 and is associated with liver cancer stage.

机构信息

Department of Clinical Laboratory, Tianjin Medical University General Hospital Airport Site, Tianjin 300308, P.R. China.

School of Nursing, Tianjin Medical University, Tianjin 300070, P.R. China.

出版信息

Mol Med Rep. 2019 Feb;19(2):935-942. doi: 10.3892/mmr.2018.9711. Epub 2018 Nov 29.

Abstract

The importance of microRNAs (miRNAs) in cancer development has been widely recognized in recent decades. In the present study, the function and mechanism of miRNA‑363‑3p (miR‑363‑3p), formerly characterized as a tumor suppressor, in the hepatocarcinogenesis of liver cancer cells was investigated. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was applied to detect the expression of miR‑363‑3p in liver cancer tissues. Cell proliferation, survival and migration capacities were determined by MTT, colony formation and wound‑healing assays, respectively. The targeting of high mobility group AT‑hook 2 (HMGA2) mRNA by miR‑363‑3p was confirmed by bioinformatics analysis, and RT‑qPCR, luciferase reporter and western blot assays. The correlation between the expression levels of HMGA2 and miR‑363‑3p was analyzed. The RT‑qPCR results revealed that the levels of miR‑363‑3p were downregulated in liver cancer tissues. Cellular assays validated that miR‑363‑3p exerted tumor suppressing functions, including the inhibition of cell proliferation, survival and migration abilities in two liver cancer cell lines. Bioinformatics prediction and subsequent experiments demonstrated that HMGA2 was a direct target of miR‑363‑3p. Restoration of the expression of HMGA2 in miR‑363‑3p mimic‑transfected cells reversed the tumor suppressing effects caused by miR‑363‑3p. Finally, there was a significant negative correlation between the expression levels of HMGA2 and miR‑363‑3p in liver cancer tissues. miR‑363‑3p was identified as an important tumor suppressor in liver cancer via targeting HMGA2, which may have potential benefits in liver cancer therapy.

摘要

近年来,miRNAs(微小 RNA)在癌症发生发展中的重要性已得到广泛认可。本研究旨在探讨 miRNA-363-3p(miR-363-3p)在肝癌细胞肝癌发生中的作用及其机制。采用逆转录定量聚合酶链反应(RT-qPCR)检测肝癌组织中 miR-363-3p 的表达。通过 MTT、集落形成和划痕愈合实验分别检测细胞增殖、存活和迁移能力。采用生物信息学分析、RT-qPCR、荧光素酶报告基因和 Western blot 实验验证 miR-363-3p 对高迁移率族蛋白 AT-hook 2(HMGA2)mRNA 的靶向作用。分析 HMGA2 与 miR-363-3p 表达水平的相关性。结果显示,miR-363-3p 在肝癌组织中表达下调。细胞实验验证 miR-363-3p 具有抑制肝癌细胞增殖、存活和迁移的肿瘤抑制功能。生物信息学预测及后续实验表明,HMGA2 是 miR-363-3p 的直接靶基因。在 miR-363-3p 模拟物转染细胞中恢复 HMGA2 的表达,可逆转 miR-363-3p 引起的肿瘤抑制作用。最后,肝癌组织中 HMGA2 与 miR-363-3p 的表达水平呈显著负相关。miR-363-3p 通过靶向 HMGA2 抑制肝癌细胞的增殖、存活和迁移,从而发挥抑癌作用,可能为肝癌治疗提供新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2173/6323225/b05cf79106f5/MMR-19-02-0935-g00.jpg

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