Effect of MicroRNA-30e on the Behavior of Vascular Smooth Muscle Cells via Targeting Ubiquitin-Conjugating Enzyme E2I

Abstract

Background: Many microRNAs (miRNAs) have recently been shown to demonstrate critical roles in differentiation, proliferation and migration of vascular smooth muscle cells (VSMCs). Methods and Results:In this study, a certain amount of miRNA expression in VSMCs was evaluated by real-time polymerase chain reaction, and it was found that microRNA-30e (miR-30e) was expressed more strongly than other common vascular well-expressed miRNAs in vitro. Subsequently, both a gain and loss of function study was performed in vitro and in vivo. It was found that miR-30e in VSMCs was strongly downregulated concomitantly with stimulation, and miR-30e inhibited VSMCs proliferation and migration both in vitro and in vivo. Furthermore, ubiquitin-conjugating enzyme E2I (Ube2i) was identified as the target gene of endogenous miR-30e by luciferase reporter assay, and it was confirmed that overexpression of miR-30e significantly reduced Ube2i and inhibited the phenotypic switch of VSMCs. Knockdown of Ube2i had an influence over the proliferation and migration of cultured VSMCs, as same as the miR-30e mimic did. Overexpression of miR-30e induced the apoptosis of VSMCs and deregulated the protein expression of IkBα, which is crucial for the NFκB signal pathway. Conclusions:The results of this study indicated that miR-30e in VSMCs exerted an anti-atherosclerosis effect via inhibiting proliferation and migration, and promoting apoptosis of VSMCs. More specifically, it was demonstrated that miR-30e exhibited these effects on VSMCs partially through targeting Ube2i and downregulating the IκBα/NFκB signaling pathway.

MiR-30e-5p and MiR-15a-5p Expressions in Plasma and Urine of Type 1 Diabetic Patients With Diabetic Kidney Disease

“…Important roles for sumoylation were shown in heterochromatin configuration, and sumoylation of core histones negatively regulates transcription (Neyret-Kahn et al, 2013). MiR-30e-5p-induced downregulation of UBE2I inhibited the proliferation and migration of vascular smooth muscle cells (Zong et al, 2017). MUC17 is a glycoprotein characterized as a membrane-bound mucin that provides protection to gut epithelial cells (Gum et al, 2002; Luu et al, 2010).…”

The Role of SGLT2 Inhibitors in Vascular Aging

“…MiR-34a not only down-regulates Silent Information Regulator 2 homolog 1, but also promotes the expression of age-related pro-inflammatory secretory factors, thereby promoting VSMC aging [ 13 ]. Reports have also indicated that miR-23 cluster can regulate blood vessel formation [ 14 ], while miR-30e can inhibit proliferation and migration of VSMCs, promote the apoptosis thereof, and exert anti-atherosclerosis effects [ 15 ]. Moreover, by inhibiting autophagy of vascular endothelial cells and promoting cell apoptosis, miR-199a-5p has been revealed to damage vascular endothelial cells and aggravate vascular aging [ 16 ].…”

Expression and Functional Analysis of lncRNAs Involved in Platelet-Derived Growth Factor-BB-Induced Proliferation of Human Aortic Smooth Muscle Cells

“…From the identified DELs, we analyzed 33 DELs containing Argonaute 2 (AGO2) binding sites, so these lncRNAs might Construction of DELs-miRNAs interaction networks (Figure 6), indicated that HIF1A-AS2 might sponge 187 miRNAs, including miR-30e-5p (18)(19)(20), miR-25-3p (21), miR-200c-3p (5), miR-490-3p (22), and miR-34b-5p (23); these five miRNAs are demonstrated to suppress VSMC proliferation (Figure 6A). AC016747.3 might sponge 41 miRNAs, including miR-342-3p (24) that has been shown to inhibit VSMC proliferation (Figure 6B).…”