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.

Clinical Parameters and Epigenetic Biomarkers of Plaque Vulnerability in Patients with Carotid Stenosis

“…miR-92a has also shown higher plasma levels in symptomatic versus asymptomatic patients [84] as has been described in the previous paragraph, suggesting that the circulating concentration of miR-92a may gradually increase from healthy subjects to asymptomatic and symptomatic patients. Moreover, miR-342-5p was significantly overexpressed in asymptomatic serum patients, which positively correlates with IL-6 and TNFα and might be involved in the proliferation and differentiation of VSMCs downregulating PI3K regulatory subunit α (PI3KR1) [69,91]. On the other hand, miR-9-5p [75], miR-503-5p [92], and miR-28-5p [93] were significantly decreased in the serum of ACAS patients.…”

The wonder exerkines—novel insights: a critical state-of-the-art review

“…On the detrimental side of the coin, serum miR-342-5p has been suggested as a biomarker for adverse cardiovascular events [ 34 , 35 ]. Indeed, miR-342-5p may promote cell proliferation, migration and invasion of vascular smooth muscle cells, via the Akt signaling pathway [ 36 ]. On the bright side, miR-342-5p modulates the cardioprotective effect by inhibiting cardiomyocyte apoptotic signal mediated by Caspase 9 and c-Jun N-terminal kinase 2 (Jnk2) and enhances survival signaling (p-Akt) in the ischemic heart [ 33 ].…”