lncRNA RBM5‐AS1 promotes cell proliferation and invasion by epigenetically silencing miR‐132/212 in hepatocellular carcinoma cells

• Published in: Cell biology international 2021-11, Vol.45 (11), p.2201-2210
• Main Authors: Mu, Jin‐Yong, Tian, Jun‐Xiu, Chen, Ying‐Jie
• Format: Article
• Language: English
• Subjects: Antitumor activity; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cholecystokinin; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epigenesis, Genetic - genetics; Epigenetics; Gene Expression - genetics; Gene Expression Regulation, Neoplastic - genetics; Hep G2 Cells; Hepatocellular carcinoma; Humans; Immunoprecipitation; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; lncRNA RBM5‐AS1; Metastases; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐132/212; Neoplasm Invasiveness - genetics; PRC2; RNA, Antisense - genetics; RNA, Long Noncoding - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Signal Transduction - genetics; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.11649

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.