Circular RNA circCHFR Facilitates the Proliferation and Migration of Vascular Smooth Muscle via miR-370/FOXO1/Cyclin D1 Pathway

Abstract

Circular RNA (circRNA) is a novel subgroup of noncoding RNA in the human transcriptome playing a vital role in the atherosclerosis of cerebrovascular disease. However, the in-depth mechanism by which circRNA regulates the vascular smooth muscle proliferation and migration is still elusive. Here, a novel identified circRNA, circCHFR, was validated to be aberrantly overexpressed in the ox-LDL-induced vascular smooth muscle cell (VSMCs). Functionally, the circCHFR silencing by oligonucleotide transfection suppressed the proliferation and migration ability of VSMCs. Mechanically, bioinformatics tools and luciferase reporter assay state that circCHFR acts as a sponge of miR-370, and miR-370 targets the 3′ UTR of FOXO1. Furthermore, the transcription factor FOXO1 could bind with the promoter region of CCND1 mRNA and promote Cyclin D1 expression. In summary, this finding states the vital role of the circCHFR/miR-370/FOXO1/Cyclin D1 axis and provides a profound understanding about the circRNA in smooth muscle cells and atherosclerosis.

Circular RNA circ_0010283 regulates the viability and migration of oxidized low‑density lipoprotein‑induced vascular smooth muscle cells via an miR‑370‑3p/HMGB1 axis in atherosclerosis

“…Zhou et al (10) have reported that circular RNA hsa_circ_0016070 is associated with pulmonary arterial hypertension. In addition, circRNA antisense non-coding RNA in the INK4 locus and circRNA checkpoint with forkhead and ring finger domains (circcHFR) have been confirmed to modulate the progression of atherosclerosis (11,12). In the present study, the expression of circ_0010283 was elevated in ox-LdL-induced VSMcs compared with that in non-induced cells, which was also supported by the microarray results of a previous study (12).…”

“…In addition, circRNA antisense non-coding RNA in the INK4 locus and circRNA checkpoint with forkhead and ring finger domains (circcHFR) have been confirmed to modulate the progression of atherosclerosis (11,12). In the present study, the expression of circ_0010283 was elevated in ox-LdL-induced VSMcs compared with that in non-induced cells, which was also supported by the microarray results of a previous study (12). In addition, the results of the present study demonstrated that circ_0010283 was induced by ox-LdL in a time-and concentration-dependent manner in VSMcs, suggesting that circ_0010283 may be associated with the progression of atherosclerosis.…”

“…Numerous studies have demonstrated that circRNAs are associated with cardiac repair (8), silica-induced macrophage activation (9), pulmonary arterial hypertension (10) and atherosclerosis (11). Microarray analysis has revealed that circ_0010283 is upregulated in oxidized low-density lipoprotein (ox-LdL)-induced VSMcs (12). However, the regulatory mechanism of circ_0010283 in atherosclerosis needs to be further investigated.…”

The potential roles of circular RNAs in osteonecrosis of the femoral head (Review)

“…one study reported that circrna e3 ubiquitin-protein ligase cHFr serves as a sponge for mir-370, which typically targets forkhead box protein (FoX)o1, and FoXo1 promotes the expression of cyclin d1 to drive the migration and proliferation of vascular smooth muscle cells. This provides an example of a profound role that circrnas can serve in cardiovascular diseases (33). in addition, there are a number of overlapping binding sites between circrnas and mirnas, and a single circrna can possibly interact with several mirnas.…”

Advances in Research on the circRNA‐miRNA‐mRNA Network in Coronary Heart Disease Treated with Traditional Chinese Medicine

“…Circ-SATB2 can regulate vascular smooth muscle cell phenotypic differentiation, proliferation, apoptosis, and migration by promoting the expression of STIM1 (a target gene of miR-939) [60]. CircCHFR facilitates the proliferation and migration of vascular smooth muscle via the miR-370/FOXO1/cyclin D1 pathway [61]. CircSlc8a1 can function as an endogenous sponge for miR-133a in cardiomyocytes, and it can regulate the serum response factor, connective tissue growth factor, adrenoceptor beta 1, and adenylate cyclase 6 through directly intervening the knockdown and overexpression in heart failure [62].…”