MicroRNA-342-5p activates the Akt signaling pathway by downregulating PIK3R1 to modify the proliferation and differentiation of vascular smooth muscle cells.

Abstract

Abnormal cell proliferation and invasion of vascular smooth muscle cells are among the primary causes of cardiovascular disease. Studies have shown that microRNA(miR)-342-5p participates in the development of cardiovascular diseases. The current study aimed to explore the role of miR-342-5p in the proliferation and differentiation of mouse aortic vascular smooth muscle (MOVAS) cells. MOVAS cells were transfected with miR-342-5p mimics, miR-342-5p inhibitor or their respective negative controls, and co-transfected with small interfering (si)RNA targeting phosphatidylinositol 3-kinase regulatory subunit α (PIK3R1) and miR-342-5p inhibitor. The cell proliferation of MOVAS cells was detected using the Cell Counting Kit-8, while cell migration and cell invasion were investigated using a wound healing and Transwell assays, respectively. Target genes for miR-342-5p were confirmed using reverse transcription-quantitative PCR (RT-qPCR) and dual luciferase reporter assay. The relative mRNA and protein expression levels of miR-342-5p were measured using RT-qPCR and western blot analysis. MOVAS cells were treated with a PI3K inhibitor (LY294002) to explore the role of miR-342-5p on the Akt pathway. The results revealed that miR-342-5p mimics promoted cell viability, migration and invasion, and increased the expression of vimentin and phosphorylated-Akt but reduced a-smooth muscle actin (α-SMA) and PIK3R1 expression. However, miR-342-5p inhibitor produced the opposite effects. PIK3R1 was the target gene for miR-342-5p and the effect of siPIK3R1 on MOVAS cells was similar to that of miR-342-5p mimics, while siPIK3R1 partially reversed the effect of miR-342-5p inhibitor on MOVAS cells. The Akt signaling pathway was activated by miR-342-5p mimics or siPIK3R1. Moreover, miR-342-5p mimics partially activated the Akt signaling pathway inhibited by LY294002. MiR-342-5p could promote the proliferation and differentiation of MOVAS and phenotypic transformation. The mechanism behind these processes may be associated with the activation of the Akt signaling pathway induced by PIK3R1 inhibition.