LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

Yaqing Zhou; Sheng Zhang; Wenfeng Ji; Xiongkang Gan; Lei Hua; Can Hou; Jiaxin Chen; Yanjun Wang; Shu He; Hanxiao Zhou; Enzhi Jia

doi:10.3389/fcell.2021.656636

LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

Front Cell Dev Biol. 2021 May 18:9:656636. doi: 10.3389/fcell.2021.656636. eCollection 2021.

Authors

Yaqing Zhou¹, Sheng Zhang¹, Wenfeng Ji¹, Xiongkang Gan¹, Lei Hua¹, Can Hou¹, Jiaxin Chen¹, Yanjun Wang¹, Shu He¹, Hanxiao Zhou¹, Enzhi Jia¹

Affiliation

¹ Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Abstract

We aimed to investigate differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in atherosclerosis and validate the expression of lncRNAs and co-expressed target genes in proliferation and migration models of human coronary artery smooth muscle cells (HCASMCs). Ten coronary artery specimens from a subject who died from a heart attack were employed. The pathological analysis was analyzed by hematoxylin and eosin (H&E) staining, and the lncRNAs and mRNAs were identified by RNA sequencing. Bioinformatic analyses were performed to predict possible mechanisms. The proliferation and migration of HCASMCs were induced with oxidized low-density lipoprotein (ox-LDL). Differentially expressed lncRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, 68 lncRNAs and 222 mRNAs were identified differentially expressed in atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the Fanconi anemia pathway may be involved in atherosclerosis. GON4L was found to be the co-localized target gene of LNC_000439, and 14 genes had high correlations with the expression of seven lncRNAs. In addition, nine lncRNA-miRNA-mRNA networks were constructed, and 53 co-expressed gene modules were detected with weighted gene co-expression network analysis (WGCNA). LNC_000684, LNC_001046, LNC_001333, LNC_001538, and LNC_002115 were downregulated, while LNC_002936 was upregulated in proliferation and migration models of HCASMCs. In total, six co-expressed mRNAs were upregulated in HCASMCs. This study suggests that the differentially expressed lncRNAs identified by RNA sequencing and validated in smooth muscle cells may be a target for regulating HCASMC proliferation and migration in atherosclerosis, which will provide a new diagnostic basis and therapeutic target for the treatment of cardiovascular diseases.

Keywords: RNA sequencing; coronary artery; coronary heart disease; long non-coding RNA; smooth muscle cell.