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

Abstract

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.

Implications in Cancer of Nuclear Micro RNAs, Long Non-Coding RNAs, and Circular RNAs Bound by PRC2 and FUS

“…Hepatocellular carcinoma is regarded as one of the most common malignancies leading to cancer-related death worldwide. The function of the lncRNA RBM5-AS1 (RBM5 antisense RNA 1) in the development of hepatocellular carcinoma was studied [ 120 ]. RBM5-AS1 levels are high in hepatocellular carcinoma tissues and cell lines, especially in Hep3B and HepG2 cells.…”

Mechanism of HBx carcinogenesis interaction with non-coding RNA in hepatocellular carcinoma

“…Among them, circular RNA (circRNA) also participates in the regulation of many processes in the onset and development of HBV-related HCC, such as the regulation of multiple key signaling pathways ( 19 ), or processes affecting liver inflammatory fibrosis and the immunosuppressive microenvironment ( 20 ). Normal lncRNAs also participate in a variety of carcinogenic mechanisms in HBV-related HCC, such as chromatin modification ( 21 ), regulation of transcriptional expression by transcription factors ( 22 ), modulation of protein stability ( 23 ), epigenetic silencing ( 24 ), mRNA splicing, and HBx-mediated lncRNA aberration ( 25 ). CircRNA, as an lncRNA with a circular structure, plays a unique role in HBV-related HCC due to its stable circular structure.…”

The RNA-Binding Motif Protein Family in Cancer: Friend or Foe?

“…RBM5-AS1 can be used as an oncogenic factor in multiple cancers, such as hepatocellular carcinoma, osteosarcoma, and oral squamous cell carcinoma. Mu et al showed that RBM5-AS1 could decrease miR-132/212 by recruit PRC2 complex, and facilitate HCC cell migration and invasion (59). Fu et al found that RBM11 was highly expressed in ovarian cancer and could promote tumor cell invasion and metastasis by activating Akt/mTOR signaling (60).…”

“…Mu et al. showed that RBM5-AS1 could decrease miR-132/212 by recruit PRC2 complex, and facilitate HCC cell migration and invasion ( 59 ). Fu et al.…”