Identification of Differently Expressed mRNAs in Atherosclerosis Reveals CDK6 Is Regulated by circHIPK3/miR-637 Axis and Promotes Cell Growth in Human Vascular Smooth Muscle Cells

Abstract

Atherosclerosis is the leading cause of heart disease and stroke, and one of the leading causes of death and disability worldwide. The phenotypic transformation of vascular smooth muscle cells (VSMCs) plays an important role in the pathological process of atherosclerosis. The present study aimed to identify differently expressed mRNAs in atherosclerosis by analyzing GSE6088 database. Our results revealed there were totally 467 increased and 490 decreased differential expressed genes (DEGs) in atherosclerosis. Bioinformatics analysis demonstrated that the DEGs substantially existed in pathways, including Glyoxylate and dicarboxylate metabolism, Tyrosine metabolism, Tryptophan metabolism, Beta-Alanine metabolism, Fatty acid biosynthesis and Starch and sucrose metabolism. Next, we constructed a protein-protein interaction (PPI) network to identify hub genes in atherosclerosis. Also, we identified CDK6 as a key regulator of atherosclerosis. In this study, we found that CDK6 knockdown suppressed HASMC and HUASMC cell proliferation. Circular RNA (CircRNA) is a non-coding RNA which is reported to have an unusual influence on tumorigenesis process and other aspects in the last few years. Previous studies showed circRNAs could act as miRNAs sponging in multiple biological processes. Bioinformatics prediction and luciferase analysis showed that CDK6 were targeted and regulated by circHIPK3/miR-637. Moreover, silencing circHIPK3 could also significantly induce the arrest and apoptosis of cell cycle. In conclusion, this study discovered the important regulatory role of circHIPK3 in the proliferation and apoptosis of VSMCs by influencing the miR-637/CDK6 axis.