Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies worldwide leading to cancer-related death. Long noncoding RNAs (lncRNAs) are a critical modulator affecting HCC progression. Whereas, the pathogenesis of lncRNA RBM5-AS1 in the development of HCC remains unclear. Quantitative RT-PCR or western blot assays were applied to detect the expression of genes and proteins, respectively. The proliferation and metastasis abilities were assessed using Cell counting kit-8 (CCK-8), EdU and transwell assays. RNA immunoprecipitation (RIP) experiment was employed to validate the molecular interactions. RBM5-AS1 is highly expressed in HCC tissues and cell lines, especially in Hep3B and HepG2 cells. RBM5-AS1 knockdown dramatically restrains cell proliferation, invasion and migration of HCC cells. Importantly, RBM5-AS1 acts as an epigenetic regulator to elevate the H3K27me3 level of miR-132/212 promoter regions via recruiting PRC2 (EZH2, SUZ12, EED), and eventually reducing miR-132/212 expressions. The recovery experiments demonstrated that downregulation of miR-132/212 markedly eliminate the antitumor effects mediated by RBM5-AS1 silencing in HCC cells. The data of this work illustrate that RBM5-AS1 acts as an epigenetic regulator to promote the HCC progression by repressing miR-132/212 expressions, which would provide a new insight for understanding the action mechanism of RBM5-AS1 in HCC development.

中文翻译：

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lncRNA RBM5-AS1通过表观遗传沉默肝细胞癌细胞中的miR-132/212促进细胞增殖和侵袭

肝细胞癌（HCC）被认为是全球最常见的导致癌症相关死亡的恶性肿瘤之一。长链非编码 RNA (lncRNA) 是影响 HCC 进展的关键调节剂。然而，lncRNA RBM5-AS1 在 HCC 发展中的发病机制仍不清楚。定量 RT-PCR 或蛋白质印迹分析分别用于检测基因和蛋白质的表达。使用细胞计数试剂盒 8 (CCK-8)、EdU 和 transwell 测定法评估增殖和转移能力。RNA免疫沉淀（RIP）实验用于验证分子相互作用。RBM5-AS1 在 HCC 组织和细胞系中高度表达，特别是在 Hep3B 和 HepG2 细胞中。RBM5-AS1 敲低可显着抑制 HCC 细胞的增殖、侵袭和迁移。重要的，RBM5-AS1 作为表观遗传调节因子通过招募 PRC2（EZH2、SUZ12、EED）来提高 miR-132/212 启动子区域的 H3K27me3 水平，并最终降低 miR-132/212 的表达。恢复实验表明 miR-132/212 的下调显着消除了 HCC 细胞中 RBM5-AS1 沉默介导的抗肿瘤作用。这项工作的数据表明，RBM5-AS1作为表观遗传调节因子通过抑制miR-132/212的表达来促进HCC的进展，这将为理解RBM5-AS1在HCC发展中的作用机制提供新的见解。恢复实验表明 miR-132/212 的下调显着消除了 HCC 细胞中 RBM5-AS1 沉默介导的抗肿瘤作用。这项工作的数据表明，RBM5-AS1作为表观遗传调节因子通过抑制miR-132/212的表达来促进HCC的进展，这将为理解RBM5-AS1在HCC发展中的作用机制提供新的见解。恢复实验表明 miR-132/212 的下调显着消除了 HCC 细胞中 RBM5-AS1 沉默介导的抗肿瘤作用。这项工作的数据表明，RBM5-AS1作为表观遗传调节因子通过抑制miR-132/212的表达来促进HCC的进展，这将为理解RBM5-AS1在HCC发展中的作用机制提供新的见解。