PDF(Pubmed)
Abstract：
Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide. Brahma-related gene 1 (BRG1), as a catalytic ATPase, is a major regulator of gene expression and is known to mutate and overexpress in HCC. The purpose of this study was to investigate the mechanism of action of BRG1 in HCC cells. In our study, BRG1 was silenced or overexpressed in human HCC cell lines. Transwell and wound healing assays were used to analyze cell invasiveness and migration. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) detection were used to evaluate mitochondrial function in HCC cells. Colony formation and cell apoptosis assays were used to evaluate the effect of BRG1/TOMM40/ATP5A1 on HCC cell proliferation and apoptosis/death. Immunocytochemistry (ICC), immunofluorescence (IF) staining and western blot analysis were used to determine the effect of BRG1 on TOMM40, ATP5A1 pathway in HCC cells. As a result, knockdown of BRG1 significantly inhibited cell proliferation and invasion, promoted apoptosis in HCC cells, whereas BRG1 overexpression reversed the above effects. Overexpression of BRG1 can up-regulate MMP level, inhibit mPTP opening and activate TOMM40, ATP5A1 expression. Our results suggest that BRG1, as an oncogene, promotes HCC progression by regulating TOMM40 affecting mitochondrial function and ATP5A1 synthesis. Targeting BRG1 may represent a new and effective way to prevent HCC development.
摘要：
肝细胞癌（HCC）是世界上最致命的恶性肿瘤之一。婆罗门相关基因1（BRG1），作为催化ATP酶，是基因表达的主要调节因子，已知在HCC中突变和过表达。目的探讨BRG1在肝癌细胞中的作用机制。在我们的研究中,BRG1在人HCC细胞系中沉默或过表达。使用Transwell和伤口愈合测定来分析细胞侵袭和迁移。线粒体膜电位（MMP）和线粒体通透性转换孔（mPTP）检测用于评估HCC细胞的线粒体功能。集落形成和细胞凋亡测定用于评估BRG1/TOMM40/ATP5A1对HCC细胞增殖和凋亡/死亡的影响。免疫细胞化学(ICC),免疫荧光（IF）染色和蛋白质印迹分析用于确定BRG1对HCC细胞中TOMM40，ATP5A1通路的影响。因此,敲低BRG1显著抑制细胞增殖和侵袭,促进肝癌细胞凋亡，而BRG1过表达逆转了上述效应。BRG1过表达可上调MMP水平,抑制mPTP开放并激活TOMM40、ATP5A1表达。我们的结果表明，BRG1作为一种癌基因，通过调节影响线粒体功能和ATP5A1合成的TOMM40促进HCC进展。靶向BRG1可能是预防HCC发展的一种新的有效方法。
