Circ_0021155 can participate in the phenotypic transformation of human vascular smooth muscle cells via the miR-4459/TRPM7 axis

TRPM7型 卡尔波宁 血管平滑肌 竞争性内源性RNA 表型 细胞生长 免疫印迹 细胞生物学 分子生物学 转化(遗传学) 化学 生物 肌动蛋白 核糖核酸 基因 平滑肌 生物化学 受体 内分泌学 瞬时受体电位通道 长非编码RNA
作者
Jinghan Lin,Chang Liu,Jing xu,Shuang Li,Dawei Dai,Liming Zhang,Pan Yonghui
出处
期刊:Biochemical and Biophysical Research Communications [Elsevier BV]
卷期号:630: 133-142
标识
DOI:10.1016/j.bbrc.2022.08.065
摘要

The phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a key role in the pathological process of atherosclerosis (AS), and TRPM7 is involved in this process. In this study, we verified whether circRNAs participate in the phenotypic transformation of VSMCs by regulating TRPM7 in AS. The RNA-sequencing data of atherosclerosis were downloaded and analysed from the GEO database. Only hsa_circ_0021155 related to TRPM7 was differentially expressed in AS. circRNA distribution and expression were observed via FISH and PCR. CCK8, scratch test and Transwell assay were used to observe the proliferation and migration of cells. Western blot was performed to examine changes in α-actin, calponin , SMMHC and TRPM7 proteins. The expression of hsa_circ_0021155 against has-miR-4459/miR-3689c was verified via PCR. The ceRNA relationship of TPRM7–miR4459–circ0021155 was verified via dual luciferase assay, and the effects of miR4459 mimic/inhibitor on the proliferation of cells were further observed. The expression of hsa_circ_0021155 and OX-LDL was increased in VSMCs. hsa_circ_0021155 promoted the expression of TRPM7 and inhibited the protein expression of α-actin, calponin and SMMHC. In addition, it promoted the proliferation and migration of cells and inhibited the expression of miR-3689c and miR-4459 but did not affect miR-4756–5p. The dual luciferase assay showed that circ0021155–miR4459–TRPM7 mRNA was highly compatible and could be mutually regulated by a ceRNA network. In conclusion, hsa_circ_0021155 regulates the proliferation, migration and phenotype transformation of VSMCs induced by OX-LDL via the miR-4459/TRPM7 axis. hsa_circ_0021155 and TRPM7 may offer novel therapeutic targets for atherosclerosis. • The phenotypic transformation of vascular smooth muscle cells involved in TRPM7 plays a key role in the pathological process of atherosclerosis. • Hsa_circ_0021155 shares interacting miRNAs with TRPM7, namely miR-3689c, miR-4756–5p and miR-4459 through biological information analysis. • Hsa_circ_0021155 promoted the proliferation and migration of HASMCs and decreased the expression of α-actin, calponin and SMMHC. • Hsa_circ_0021155 may regulate the proliferation and migration of HASMCs through miR-4459.

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