CircRBM23 regulates the switch between osteogenesis and adipogenesis of mesenchymal stem cells via sponging miR-338-3p.

BACKGROUND: The disruption of the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in bone marrow contributes to the adipocytes accumulation and bone loss, which leads to the development of osteoporosis (OP). The circular RNA (circRNA), circRBM23, was generated from the RNA binding motif protein 23 (RBM23) gene. It was reported that circRBM23 was down-regulated in OP patients, but it remains unknown whether its down-regulation is involved in the lineage switch of MSCs. OBJECTIVE: We aimed to explore the role and mechanism of circRBM23 in regulating the switch between osteogenic and adipogenic differentiation of MSCs. METHODS: The expression and function of circRBM23 in vitro were detected by qRT-PCR, alizarin red staining, and oil Red O staining. The interactions between circRBM23 and microRNA-338-3p (miR-338-3p) were analyzed by RNA pull-down assay, FISH, and dual-luciferase reporter assay. MSCs treated with lentivirus overexpression of circRBM23 was applied for both in vitro and in vivo experiments. RESULTS: CircRBM23 was expressed at lower levels in OP patients. Besides, circRBM23 was up-regulated during osteogenesis and down-regulated during adipogenesis of MSCs. CircRBM23 could promote the osteogenic differentiation but inhibit the adipogenic differentiation of MSCs. Mechanistically, circRBM23 acted as a sponge for microRNA-338-3p (miR-338-3p) to enhance the expression of RUNX family transcription factor 2 (RUNX2). CONCLUSIONS: Our research indicates that circRBM23 could promote the switch from adipogenic to osteogenic differentiation of MSCs via sponging miR-338-3p. It might improve the understanding of the lineage switch of MSCs and provide a potential target for diagnosing and treating OP.

Effects of hsa_circRBM23 on Hepatocellular Carcinoma Cell Viability and Migration as Produced by Regulating miR-138 Expression.

Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors. At present, the molecular mechanism of HCC remains unclear. A recent circular RNA (circRNA) profiling study showed that circRBM23 expression was upregulated in HCC tissues. Therefore, in this study, the impact of circRBM23 during the progression of HCC was evaluated. The expression levels of circRBM23 and miR-138 in HCC tissues and HCC cell lines were determined by RT-PCR and the results indicated that circRBM23 expression was increased in the HCC tissues and HCC cell lines, whereas miR-138 expression was decreased. An upregulation of circRBM23 expression in HCC cells was shown to increase cell viability, and also increased the ability of cells to migrate. Downregulation of circRBM23 was found to decrease cell viability, proliferation, and migration, and promote the expression of miR-138 and its related target genes, vimentin, and CCND3. Moreover, miR-138 was found to regulate HCC cell viability and migration, and the levels of vimentin and CCND3 protein expression were found to be inversely correlated with those of miR-138 expression. The downregulation of circRBM23 in HCC tissues can regulate the miR-138-mediated signal pathway by promoting miR-138 expression. The results in vivo demonstrated that circRBM23 is required for the tumorigenesis with downregulation of tumor suppressor miR-138. These data indicated that upregulated circRBM23 functioned as oncogene in HCC through regulating the tumor suppressor miR-138.