MiR-363-3p inhibits rat lung alveolar type II cell proliferation by downregulating STRA6 expression and induces cell apoptosis via cellular oxidative stress and G1-phase cell cycle arrest.

Abstract

BackgroundmiR-363-3p, the retinoid signaling pathway (RSP), and its associated membrane receptor, stimulated by retinoic acid 6 (STRA6), participate in lung development. We hypothesize that miR-363-3p is involved in lung cell proliferation and apoptosis by regulating the expression of STRA6, and this study was designed to investigate the effect of changes in the expressions of miR-363-3p and the STRA6 gene on the proliferation and apoptosis of rat alveolar type II cells.MethodsTo confirm our hypothesis, we used: a dual-luciferase reporter assay; cell culture and transfection; real-time quantitative polymerase chain reaction (PCR); Western blotting; a cell proliferation assay and flow cytometry analysis of the cell cycle, cell apoptosis, oxidative stress level, and mitochondrial membrane potential.ResultsOur results showed that STRA6 is a target gene for miR-363-3p, and when the expression of miR-363-3p increased, the relative messenger RNA (mRNA) expression of STRA6 decreased, which caused a decrease in STRA6 protein synthesis and subsequent inhibition of rat lung alveolar type II cell proliferation. In contrast, inhibiting the expression of miR-363-3p promoted the proliferation of these cells. This study also found that an increased expression of miR-363-3p induced rat lung alveolar type II cell apoptosis led to an increase in the oxidative stress level, decreased mitochondrial membrane potential, and an inducement of G1-phase cell cycle arrest.ConclusionsIn conclusion, miR-363-3p is associated with lung cell proliferation and apoptosis, while miR-363-3p inhibits rat lung alveolar type II cell proliferation by downregulating the expression of STRA6 and induces cell apoptosis by increasing cellular oxidative stress and G1-phase cell cycle arrest.