Expression and Functional Analysis of lncRNAs Involved in Platelet-Derived Growth Factor-BB-Induced Proliferation of Human Aortic Smooth Muscle Cells.

Jia-Jie Lin,Ke-Xin Liu,Bin Li,Kun Liu,Peng Kong,Yu Wang,Li-Hua Dong,Miao Gong,Mei-Yang Du,Xin Xu,Wei Chen,Li-Yun Yang,Shao-Guang Sun,Si-Fan Wang,Yi-Ming Li

doi:10.3389/fcvm.2021.702718

Abstract

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of many vascular remodeling diseases. Because long non-coding RNAs (lncRNAs) play a critical role in cardiovascular diseases, we analyzed the key lncRNAs that regulate VSMC proliferation. Microarray analysis identified 2,643 differentially expressed lncRNAs (DELs) and 3,720 differentially expressed coding genes (DEGs) between fetal bovine serum (FBS) starvation-induced quiescent human aortic smooth muscle cells (HASMCs) and platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferative HASMCs. Gene Ontology and pathway analyses of the identified DEGs and DELs demonstrated that many lncRNAs were enriched in pathways related to cell proliferation. One of the upregulated lncRNAs in proliferative HASMC was HIF1A anti-sense RNA 2 (HIF1A-AS2). HIF1A-AS2 suppression decreased HASMC proliferation via the miR-30e-5p/CCND2 mRNA axis. We have thus identified key DELs and DEGs involved in the regulation of PDGF-BB induced HASMC proliferation. Moreover, HIF1A-AS2 promotes HASMC proliferation, suggesting its potential involvement in VSMC proliferative vascular diseases.

Highlights

Vascular smooth muscle cells (VSMCs), the main cells that constitute blood vessels, play a critical role in maintaining their normal physiological function [1]
We investigated the function of long non-coding RNAs (lncRNAs) in human aortic smooth muscle cells (HASMCs) proliferation stimulated by the growth factor platelet-derived growth factor-BB (PDGF-BB)
Our Gene Ontology (GO) and pathway analyses showed that differentially expressed coding genes (DEGs) neighboring differentially expressed lncRNAs (DELs) were enriched in the RNA-induced silencing complex (RISC; Figure 5D) that is required for miRNAs binding to target genes

Summary

Introduction

Vascular smooth muscle cells (VSMCs), the main cells that constitute blood vessels, play a critical role in maintaining their normal physiological function [1]. LncRNAs have emerged as critical regulators of LncRNAs Regulate VSMC Proliferation various VSMC functions, including proliferation, migration, and apoptosis; they act as ceRNAs to sponge miRNAs in VSMCs [7,8,9,10]. By binding miR-148b, lncRNA H19 upregulates Wnt family member 1 (WNT1), thereby facilitating proliferation and inhibiting apoptosis of VSMCs [7]. LncRNA MEG3 sponges miR-361-5p to upregulate expression of ATP-binding cassette transporter A1 (ABCA1), which inhibits proliferation and induces apoptosis of VSMCs [8]. LncRNA GAS5 binds to miR-21, relieving inhibition of programmed cell death 4 (PDCD4) and suppressing platelet-derived growth factor-BB (PDGF-BB)induced VSMC proliferation and migration [9]. LncRNA C2dat promotes expression of sirtuin 1 (SIRT1) by targeting miR-34a5p, enhancing VSMC proliferation and migration [10]

Methods

Results

Conclusion