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miR-329-3p 通过 USP22-Wnt/β-Catenin 通路抑制肝癌细胞增殖和迁移。

MiR-329-3p inhibits hepatocellular carcinoma cell proliferation and migration through USP22-Wnt/β-Catenin pathway.

机构信息

Department of Hepatobiliary Surgery, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, P.R. China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Oct;24(19):9932-9939. doi: 10.26355/eurrev_202010_23204.

DOI:10.26355/eurrev_202010_23204
PMID:33090397
Abstract

OBJECTIVE

MicroRNA-329-3p (miR-329-3p) has been shown to be involved in tumor development. But its role in hepatocellular carcinoma has not been explored. Our study aims to explore the effect and mechanism of miR-329-3p on hepatocellular carcinoma development.

PATIENTS AND METHODS

Hepatocellular carcinoma tissues and paired paracancerous specimens from 31 hepatocellular carcinoma patients undergoing surgery were collected. Quantitative real-time polymerase chain reaction and Western blot were employed to measure genes expression at mRNA and protein level. CCK-8 and transwell assays were performed to evaluate hepatocellular carcinoma cells proliferation and migration. Dual-Luciferase reporter gene assay was designed to validate the target gene of miR-329-3p.

RESULTS

Our study showed miR-329-3p expression was significantly lower in hepatocellular carcinoma tissue. MiR-329-3p mimic inhibits proliferation and migration of HepG2 cells. By using Dual-Luciferase reporter gene assay, we proved that miR-329-3p inhibited HepG2 cell proliferation and migration by targeting USP22 directly. By up- and downregulation of USP22 expression, we also proved that USP22 can activate the Wnt/β-Catenin pathway, which in turn affected the proliferation and migration of HepG2 cells.

CONCLUSIONS

We demonstrated that miR-329-3p can inhibit HepG2 cell proliferation and migration by inhibiting USP22-Wnt/β-Catenin pathway. Our study provides novel insights into the aetiology and potential treatment of hepatocellular carcinoma.

摘要

目的

MicroRNA-329-3p(miR-329-3p)已被证明参与肿瘤的发生。但它在肝细胞癌中的作用尚未被探索。我们的研究旨在探讨 miR-329-3p 对肝细胞癌发展的影响及其机制。

患者和方法

收集 31 例接受手术的肝细胞癌患者的肝癌组织和配对癌旁标本。采用实时定量聚合酶链反应和 Western blot 检测基因在 mRNA 和蛋白水平的表达。CCK-8 和 Transwell 实验分别用于评估肝癌细胞的增殖和迁移。双荧光素酶报告基因实验用于验证 miR-329-3p 的靶基因。

结果

本研究显示 miR-329-3p 在肝癌组织中的表达明显降低。miR-329-3p 模拟物抑制 HepG2 细胞的增殖和迁移。通过双荧光素酶报告基因实验,我们证明 miR-329-3p 通过直接靶向 USP22 抑制 HepG2 细胞的增殖和迁移。通过上调和下调 USP22 的表达,我们还证明 USP22 可以激活 Wnt/β-Catenin 通路,进而影响 HepG2 细胞的增殖和迁移。

结论

我们证明 miR-329-3p 可以通过抑制 USP22-Wnt/β-Catenin 通路抑制 HepG2 细胞的增殖和迁移。我们的研究为肝细胞癌的病因学和潜在治疗提供了新的见解。

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