miR-3682-3p 通过调控 PTEN/PI3K/AKT/β-连环蛋白信号通路激活 c-Myc 加重肝癌细胞的迁移和干性。

miR-3682-3p Activated by c-Myc Aggravates the Migration and Stemness in Hepatocellular Carcinoma Cells by Regulating PTEN/PI3K/AKT/β-Catenin Signaling.

机构信息

Department of Gastroenterology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.

出版信息

Dig Dis. 2023;41(3):447-457. doi: 10.1159/000527800. Epub 2022 Nov 10.

DOI:10.1159/000527800

PMID:36366818

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a leading cancer worldwide. miRNA has been linked to cancer processes. We want to figure out what the underlying mechanism and functions of miR-3682-3p are in HCC.

METHODS

Thirty pairs of tumor tissues and adjacent tissues were obtained from HCC patients. mRNA and protein expressions were detected by quantitative real-time PCR and Western blot, respectively. The migration and invasion were measured using transwell or wound-healing assays. Dual luciferase and ChIP assays were utilized to detect gene interactions.

RESULTS

miR-3682-3p was highly expressed in HCC tissues and cell lines. Silencing of miR-3682-3p inhibited cell migration and invasion, increased E-cadherin expression, and decreased N-cadherin, vimentin, and snail expressions, as well as the SOX2, OCT4, and Bmi1 expression, thereby restraining EMT and stemness of HCC in vitro. miR-3682-3p was positively activated by c-Myc and could directly target PTEN to activate PI3K/AKT/β-catenin pathway. In addition, inhibition of PTEN weakened the anti-migration and anti-stemness effects of miR-3682-3p downregulation in HCC cells.

CONCLUSION

miR-3682-3p promoted HCC migration and stemness through PTEN/PI3K/AKT/β-catenin signaling, implying that miR-3682-3p might be a promising target for HCC clinical treatment.

摘要

背景

肝细胞癌（HCC）是全球主要的癌症之一。miRNA 与癌症过程有关。我们想弄清楚 miR-3682-3p 在 HCC 中的潜在机制和功能。

方法

从 HCC 患者中获得了 30 对肿瘤组织和相邻组织。通过定量实时 PCR 和 Western blot 分别检测 mRNA 和蛋白质表达。使用 Transwell 或划痕愈合测定法测量迁移和侵袭。利用双荧光素酶和 ChIP 测定来检测基因相互作用。

结果

miR-3682-3p 在 HCC 组织和细胞系中高表达。miR-3682-3p 的沉默抑制了细胞迁移和侵袭，增加了 E-钙粘蛋白的表达，降低了 N-钙粘蛋白、波形蛋白和 snail 的表达，以及 SOX2、OCT4 和 Bmi1 的表达，从而抑制了 HCC 细胞的 EMT 和干性。c-Myc 正向激活 miR-3682-3p，并能直接靶向 PTEN 激活 PI3K/AKT/β-catenin 通路。此外，抑制 PTEN 减弱了 miR-3682-3p 下调在 HCC 细胞中对迁移和干性的抑制作用。