Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging miR-124

摘要

Abstract Increasing evidences have revealed the important role of circular RNAs (circRNAs) in cardiovascular system disease. Whereas, the expression profiles and in-depth regulation of circRNAs on vascular smooth muscle cells (VSMCs) is still undetermined. In present study, our research team performed circRNAs microarray analysis to present the circRNAs expression profiles in high glucose induced VSMCs in vitro . Results showed that total of 983 circRNAs were discovered to be differentially expressed, and of these, 458 were upregulated and 525 were downregulated. Moreover, 31 circRNAs were up-regulated and 22 circRNAs were down-regulated with 2 fold change (P? vitro cell assay, circWDR77 silencing significantly inhibited the proliferation and migration. Bioinformatics methods discovered that miR-124 and fibroblast growth factor 2 (FGF-2) were downstream targets of circWDR77. The RNA sequence complementary binding was validated by RNA immunoprecipitation (RIP) and/or luciferase reporter assay. Further function validation experiments revealed that circWDR77 regulated VSMCs proliferation and migration via targeting miR-124/FGF2. Taken together, present study firstly reveals the circRNAs expression profiles in high glucose induced VSMCs and identifies the role of circWDR77-miR-124-FGF2 regulatory pathway in VSMCs proliferation and migration, which might provide a new theoretical basis for diabetes mellitus correlated vasculopathy. Highlights ? Our research team firstly screen the circular RNA expression profiles in high glucose induced VSMCs using circRNA microarray analysis. ? CircWDR77 is identified to be up-regulated in high glucose induced VSMCs. ? CircWDR77 silencing suppresses the proliferation and migration of VSMCs. ? CircWDR77 acts as an endogenous sponge of miR-124. ? CircWDR77-miR-124-FGF2 regulatory pathway play important role in VSMCs proliferation and migration.