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.

中文翻译：

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lncRNA MALAT1结合染色质重塑亚基BRG1来表观遗传地促进炎症相关的肝细胞癌的进展。

肝细胞癌（HCC）是一种癌症，其癌变和进展与慢性炎症密切相关。鉴定与炎症相关的HCC进程的分子机制将有助于提高当前疗法对HCC患者的疗效。已发现许多表观遗传因素，包括长的非编码RNA（lncRNA），在肝癌的生长和转移中起着重要的作用。但是，lncRNAs如何促进HCC进程以及lncRNA沉默在体内抑制HCC的应用仍有待进一步研究。在这里，我们发现HCC肿瘤组织中lncRNA转移相关的肺腺癌转录本（MALAT1）被上调，而MALAT1的抑制则抑制了增殖，细胞周期和对脂多糖（LPS）刺激的HCC细胞侵袭。敲低MALAT1可以显着抑制HPS细胞中LPS诱导的促炎介质IL-6和CXCL8的表达，这可以通过过表达MALAT1来恢复。机械上，MALAT1将婆罗门相关基因1（BRG1）募集到IL-6和CXCL8的启动子区域，将染色质重塑复合转换/不可发酵的蔗糖的催化亚基（SWI / SNF）募集到一起，从而促进了NF-κB诱导这些炎症因子的表达。重要的是，MALAT1在HCC组织中的体内沉默抑制了HCC异种移植物的生长，并因此也抑制了HCC组织中促炎因子的表达。