lncRNA MALAT1 binds chromatin remodeling subunit BRG1 to epigenetically promote inflammation-related hepatocellular carcinoma progression

Abstract

Hepatocellular carcinoma (HCC) is one type of cancers whose carcinogenesis and progression are closely related to chronic inflammation. Identifying the molecular mechanisms for inflammation-related HCC progression will contribute to improve the efficacy of current therapeutics for HCC patients. Many kinds of epigenetic factors, including long non-coding RNAs (lncRNAs), have been discovered to be important in HCC growth and metastasis. However, how the lncRNAs promote HCC progression and what’s the application of lncRNA silencing in vivo in suppressing HCC remain to be further investigated. Here, we found that lncRNA metastasis associated lung adenocarcinoma transcript1 (MALAT1) was upregulated in HCC tumor tissues, and knockdown of MALAT1 suppressed proliferation, cell cycle and invasion of HCC cells in response to lipopolysaccharide (LPS) stimulation. Knockdown of MALAT1 significantly inhibited LPS-induced pro-inflammatory mediators IL-6 and CXCL8 expression in HCC cells, which could be restored by overexpressing MALAT1. Mechanistically, MALAT1 recruited Brahma-related gene 1 (BRG1), a catalytic subunit of chromatin remodeling complex switching/sucrose non-fermentable (SWI/SNF), to the promoter region of IL-6 and CXCL8, and thus facilitated NF-κB to induce the expression of these inflammatory factors. Importantly, in vivo silencing of MALAT1 in HCC tissues inhibited growth of HCC xenografts, and also suppressed the expression of pro-inflammatory factors in HCC tissues accordingly. Our results demonstrate that MALAT1 promotes HCC progression by binding BRG1 to epigenetically enhance inflammatory response in HCC tissues, and silencing of MALAT1 may be a potential approach to the treatment of HCC.

Keywords

• lncrna
• inflammation and cancer
• malat1
• chromatin remodeling
• brg1
• hepatocellular carcinoma