RelB represses miR-193a-5p expression to promote the phenotypic transformation of vascular smooth muscle cells in aortic aneurysm

Abstract

Aortic aneurysm (AA) is a potentially fatal disease with the possibility of rupture, causing high mortality rates with no effective drugs for the treatment of AA. The mechanism of AA, as well as its therapeutic potential to inhibit aneurysm expansion, has been minimally explored. Small non-coding RNA (miRNAs and miRs) is emerging as a new fundamental regulator of gene expression. This study aimed to explore the role and mechanism of miR-193a-5p in abdominal aortic aneurysms (AAA). In AAA vascular tissue and Angiotensin II (Ang II)-treated vascular smooth muscle cells (VSMCs), the expression of miR-193a-5 was determined using real-time quantitative PCR (RT-qPCR). Western blotting was used to detect the effects of miR-193a-5p on PCNA, CCND1, CCNE1, and CXCR4. To detect the effect of miR-193a-5p on the proliferation and migration of VSMCs, CCK-8, and EdU immunostaining, flow cytometry, wound healing, and Transwell Chamber analysis were performed. In vitro results suggest that overexpression of miR-193a-5p inhibited the proliferation and migration of VSMCs, and its inhibition aggravated their proliferation and migration. In VSMCs, miR-193a-5p mediated proliferation by regulating CCNE1 and CCND1 genes and migration by regulating CXCR4. Further, in the Ang II-induced abdominal aorta of mice, the expression of miR-193a-5p was reduced and significantly downregulated in the serum of patients with aortic aneurysm (AA). In vitro studies confirmed that Ang II-induced downregulation of miR-193a-5p in VSMCs by upregulation of the expression of the transcriptional repressor RelB in the promoter region. This study may provide new intervention targets for the prevention and treatment of AA.