MiR-182-5p Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by ox-LDL Through Targeting PAPPA
Chaolong Jin, Shan Gao, Dayuan Li, Xuegong Shi, Zhangyue Hu, Chunmiao Wang, Jie Xiao, Zhe Sheng, Zhifeng Ding, Dingxin Zhang, Di Wang, Tingting Wang, Fang Yang, Ying Yang, Xinglong Wang, Liping Wu, Yue Xu
Abstract
This study aims to analyze the expression level and correlation of miR-182-5p and its target gene PAPPA in coronary atherosclerosis (CAD).Real time PCR, ELISA, and Western blotting methods were used to detect the expression levels. Dual-luciferase reporter gene assays were used to analyze the interaction between the 3'-UTR of PAPPA and miR-182-5p.The expression level of miR-182-5p in CAD was significantly lower than that in normal population, while the content of serum PAPPA was significantly increased, and the expression level of miR-182-5p was negatively correlated with the PAPPA content. The expression level of miR-182-5p decreased, while the expression level of PAPPA increased significantly in the ox-LDL treated HA-VSMC cells. Researchers found that PAPPA could promote the activation of IGF signaling pathway in HA-VSMC cells treated by ox-LDL, further activate NF-kB, PI3K/AKT and ERK signaling pathway, and promote cell proliferation. However, miR-182-5p could inhibit the expression of PAPPA, block the activation of IGF signal pathway, and inhibit the proliferation of HA-VSMC cells induced by ox-LDL. miR-182-5p had a targeted action site in the 3'-UTR of PAPPA by bioinformatics prediction. The analysis of luciferase reporter gene further confirmed that miR-182-5p could target the 3'-UTR of PAPPA to inhibit its expression.miR-182-5p demonstrated a protective effect on atherosclerosis and may be a potential therapeutic target for atherosclerosis.