miR-339 suppresses proliferation of pulmonary arterial smooth muscle cells via regulating IGF2BP1

AIM: The present study aimed to investigate the role of microRNA-339 miR-339 in the proliferation of pulmonary artery smooth muscle cells (PASMCs). METHODS: After treating with angiotensin Ⅱ of different concentrations for 48 h, miR-339 mimic and miR-339 inhibitor were transfected into PASMCs, respectively. CCK-8 assay and viable cell counting were performed to determine cell proliferation. The expression levels of miR-339 and PCNA mRNA were measured by RT-qPCR. The protein levels were detected by Western blot. The interaction between miR-339 and insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1) was confirmed by luciferase reporter assay. RESULTS: Angiotensin Ⅱ concentration-dependently increased cell proliferation and mRNA expression of PCNA, and decreased miR-339 expression in the PASMCs. Over-expression of miR-339 inhibited cell proliferation and mRNA expression of PCNA in the PASMCs, while mutation of miR-339 promoted cell proliferation and mRNA expression of PCNA in the PASMCs. In addition, miR-339 inhibited cell proliferation in angiotensin Ⅱ-treated PASMCs. Bioinformatics analysis showed that miR-339 targeted the IGF2BP1 3'-UTR, which was confirmed by luciferase reporter assay, and miR-339 negatively regulated the expression of IGF2BP1 in the PASMCs. More importantly, over-expression of IGF2BP1 attenuated the inhibitory effects of miR-339 on cell proliferation and mRNA expression of PCNA in the PASMCs. miR-399 over-expression suppressed phosphorylated p38 protein level but not p38 protein level. CONCLUSION: miR-339 suppresses anti-proliferative effects in PASMCs partly via regulating IGF2BP1 and p38 MAPK signaling pathway.