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ox-LDL regulates proliferation and apoptosis in VSMCs by controlling the miR-183-5p/FOXO1

福克斯O1 小RNA 生物 流式细胞术 细胞凋亡 信使核糖核酸 血管平滑肌 污渍 免疫印迹 下调和上调 转录组 内科学 分子生物学 内分泌学 基因表达 基因 生物化学 医学 蛋白激酶B 平滑肌
作者
Mingqiang Fan,Yinglong Huang,Kunsheng Li,Xiangxiang Yang,Jing Bai,Qiaoke Si,Zhengfei Peng,Chunwen Jia,Qiangnu Zhang,Ding Tao
出处
期刊:Genes & Genomics [Springer Nature]
卷期号:44 (6): 671-681 被引量:9
标识
DOI:10.1007/s13258-022-01236-x
摘要

microRNA-mRNA axes that are involved in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) proliferation/apoptosis imbalance need to be further investigated.To investigate the functional role of miR-183-5p/FOXO1 in VSMCs and its interaction with ox-LDL.RNA sequencing was used to detect transcriptome changes of VSMCs treated with ox-LDL. miR-183-5p and FOXO1 expression levels in VSMCs after ox-LDL treatment were assessed using qRT-PCR and western blotting. The regulatory effect of miR-183-5p on FOXO1 has been tried to prove using a dual-luciferase reporter assay. The functions of miR-183-5p, and FOXO1 were analyzed by CCK-8 assay and flow cytometry assay. The tissue samples or serum samples of high fat-feeding mice and carotid atherosclerosis patients were collected, and the levels of miR-183-5p/FOXO1 were analyzed.RNA sequencing data showed 81 miRNAs including miR-183-5p was significantly changed after ox-LDL treatment in VSMCs. FOXO1, a miR-183-5p's potential target, was also down-regulated in ox-LDL treated cells. qRT-PCR and western blot found that expression of FOXO1 mRNA and protein significantly reduced in VSMCs treated with ox-LDL, accompanied by overexpression of miR-183-5p. miR-183-5p inhibited FOXO1 mRNA by binding to its 3' UTR. Interference miR-183-5p/FOXO1 could change proliferation/apoptosis imbalance in VSMCs under ox-LDL stimulation. Higher levels of miR-183-5p but reduced FOXO1 can be found in the thoracic aorta tissues of high fat-feeding mice. In serum samples from individuals with carotid atherosclerosis, Higher levels of miR-183-5p were observed. the miR-183-5p level was positively related to the level of serum ox-LDL in patients.Aberrant expression of miR-183-5p/FOXO1 pathway mediated ox-LDL-induced proliferation/apoptosis imbalance in VSMCs. The miR-183-5p/FOXO1 axis can potentially be utilized as the target in the treatment of patients with atherosclerosis.
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