MicroRNA-375-3p is implicated in carotid artery stenosis by promoting the cell proliferation and migration of vascular smooth muscle cells

Abstract

Background Atherosclerosis is the main cause of carotid artery stenosis (CAS) which mostly occurs in the elderly. In this paper, the expression level of miR-375-3p in asymptomatic CAS patients and its diagnostic value for asymptomatic CAS were investigated, and the effects of miR-375-3p on the cell proliferation and migration of vascular smooth muscle cells (VSMCs) was further explored. Methods 98 healthy subjects and 101 asymptomatic CAS patients were participated in this study. qRT-PCR was used to measure the expression level of serum miR-375-3p, and the ROC curve was established to evaluate the predictive value of miR-375-3p for asymptomatic CAS. After transfection with miR-375-3p mimic or inhibitor in vitro, cell proliferation and migration were detected by CCK-8 assay, colony formation assay, and Transwell assay, respectively. The levels of TNF-α, IL-1β, IL-6 were detected by ELISA. Western blot was used to detect the protein expression of XIAP. Finally, luciferase reporter gene assay was applied to assess the interaction of miR-375-3p with target genes. Results The expression level of serum miR-375-3p in asymptomatic CAS patients was significantly higher than that in healthy controls, and the AUC value of ROC curve was 0.888. The sensitivity and specificity were 80.2 and 86.7%, respectively, indicating that miR-375-3p had high diagnostic value for asymptomatic CAS. In vitro cell experiments showed that up-regulation of miR-375-3p significantly promoted the proliferation and migration of VSMCs, and also promoted the generation of inflammatory factors and phenotypic transformation of VSMCs. Luciferase reporter gene assay confirmed that XIAP was a target gene of miR-375-3p and was negatively regulated by miR-375-3p. Conclusions In this study, miR-375-3p may have a clinical diagnostic value for asymptomatic CAS patients which need further validation. Increased miR-375-3p levels in CAS may be associated with increased proliferation and migration of VSMCs via downregulation of the apoptosis inducing gene XIAP.

PCSK9i promoting the transformation of AS plaques into a stable plaque by targeting the miR-186-5p/Wipf2 and miR-375-3p/Pdk1/Yap1 in ApoE−/− mice

“…Research has indicated its significant upregulation in AS models and its inhibition leads to reduced intracellular lipid accumulation ( 66 , 67 ). Conversely, miR-375-3p overexpression promotes endothelial cell proliferation, migration, and phenotypic transition, potentially promoting CAS development by targeting XIAP ( 68 ). Studies have shown that miR-375-3p inhibitors exert a protective effect against high glucose- or hypoxia-induced endothelial progenitor cell (EPC) injury, and enhance the antioxidant capacity in a myocardial fibroblast model ( 69 , 70 ).…”

The Expression Levels of MicroRNAs Differentially Expressed in Sudden Sensorineural Hearing Loss Patients’ Serum Are Unchanged for up to 12 Months after Hearing Loss Onset

“…The overexpression of miR-128-3p decreases VSMCs proliferation and migration and helps VSCMs maintain a contractile phenotype [ 46 ]. In contrast, miR-375-3p overexpression has been implicated in carotid artery stenosis by promoting VSMC proliferation and migration [ 47 ]. MiR-375-3p expression was also found to be downregulated in several neural injury models, including cerebral ischemia/reperfusion injury (I/RI) models [ 48 , 49 , 50 ].…”

The Effect of TNF-α on CHD and the Relationship between TNF-α Antagonist and CHD in Rheumatoid Arthritis: A Systematic Review

“…Abnormal migration, extracellular matrix synthesis, and proliferation of vascular smooth muscle cells (VSMCs) contribute to the formation of atherosclerotic plaque [65]. TNF-α causes VSMC proliferation and migration through multiple pathways [66][67][68][69][70][71]. It contains upregulated expression of lncRNA HIX003209, miR-21, lncRNA CAMK2D-associated transcript-1, miR-375-3p, Raf-1/MAPK-dependent manner, and the help of matrix metalloproteinase 2.…”