Differential Expression and Bioinformatics Analysis of CircRNA in PDGF-BB-Induced Vascular Smooth Muscle Cells

Jiangtian Tian; Yahong Fu; Qi Li; Ying Xu; Xiangwen Xi; Yuqi Zheng; Li Yu; Zhuozhong Wang; Bo Yu; Jinwei Tian

doi:10.3389/fgene.2020.00530

Differential Expression and Bioinformatics Analysis of CircRNA in PDGF-BB-Induced Vascular Smooth Muscle Cells

Front Genet. 2020 May 29:11:530. doi: 10.3389/fgene.2020.00530. eCollection 2020.

Authors

Jiangtian Tian^{1

2}, Yahong Fu^{1

2}, Qi Li^{1

3}, Ying Xu^{1

4}, Xiangwen Xi^{1

2}, Yuqi Zheng^{1

2}, Li Yu^{1

2}, Zhuozhong Wang^{1

2}, Bo Yu², Jinwei Tian²

Affiliations

¹ Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.
² Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
³ Department of Pathology, Harbin Medical University, Harbin, China.
⁴ Basic Medical College of Mudanjiang Medical College, Mudanjiang, China.

Abstract

Atherosclerosis is mediated by various factors and plays an important pathological foundation for cardiovascular and cerebrovascular diseases. Abnormal vascular smooth muscle cells (VSMCs) proliferation and migration have an essential role in atherosclerotic lesion formation. Circular RNAs (circRNA) have been widely detected in different species and are closely related to various diseases. However, the expression profiles and molecular regulatory mechanisms of circRNAs in VSMCs are still unknown. We used high-throughput RNA-seq as well as bioinformatics tools to systematically analyze circRNA expression profiles in samples from different VSMC phenotypes. Polymerase chain reaction (PCR), Sanger sequencing, and qRT-PCR were performed for circRNA validation. A total of 22191 circRNAs corresponding to 6273 genes (host genes) in the platelet-derived growth factor (PDGF-BB) treated group, the blank control group or both groups, were detected, and 112 differentially expressed circRNAs were identified between the PDGF-BB treated and control groups, of which 59 were upregulated, and 53 were downregulated. We selected 9 circRNAs for evaluation of specific head-to-tail splicing, and 10 differentially expressed circRNAs between the two groups for qRT-PCR validation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses enrichment analyses revealed that the parental genes of the circRNAs mainly participated in cardiac myofibril assembly and positive regulation of DNA-templated transcription, indicating that they might be involved in cardiovascular diseases. Finally, we constructed a circRNA-miRNA network based on the dysregulated circRNAs and VSMC-related microRNAs. Our study is the first to show the differential expression of circRNAs in PDGF-BB-induced VSMCs and may provide new ideas and targets for the prevention and therapy of vascular diseases.

Keywords: RNA-seq; VSMC; cardiovascular disease; ceRNA; circRNA.