Affiliation: | 1. Laboratory of General Surgery, Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Contribution: Data curation (lead), Writing - original draft (lead);2. Laboratory of General Surgery, Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Contribution: Investigation (lead), Methodology (lead);3. Laboratory of General Surgery, Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Contribution: Formal analysis (lead), Funding acquisition (equal);4. Laboratory of General Surgery, Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Contribution: Project administration (lead), Supervision (lead);5. Laboratory of General Surgery, Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Contribution: Writing - review & editing (lead);6. Laboratory of General Surgery, Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China |
Abstract: | Numerous microRNAs participate in regulating the pathological process of atherosclerosis. We have found miR-130a is one of the most significantly down-regulated microRNAs in arteriosclerosis obliterans. Our research explored the function of miR-130a in regulating proliferation by controlling autophagy in arteriosclerosis obliterans development. A Gene Ontology (GO) enrichment analysis of miR-130a target genes indicated a correlation between miR-130a and cell proliferation. Thus, cell cycle, CCK-8 assays and Western blot analysis were performed, and the results indicated that miR-130a overexpression in vascular smooth muscle cells (VSMCs) significantly attenuated cell proliferation, which was validated by an in vivo assay in a rat model. Moreover, autophagy is thought to be involved in the regulation of proliferation. As our results indicated, miR-130a could inhibit autophagy, and ATG2B was predicted to be a target of miR-130a. The autophagy inhibition effect of miR-130a overexpression was consistent with the effect of ATG2B knockdown. The results that ATG2B plasmids and miR-130a mimics were cotransfected in VSMCs further confirmed our conclusion. In addition, by using immunohistochemistry, the positive results of LC3 II/I and ATG2B in the rat model and artery vascular tissues from the patient were in accordance with in vitro data. In conclusion, our data demonstrate that miR-130a inhibits VSMCs proliferation via ATG2B, which indicates that miR-130a could be a potential therapeutic target that regulates autophagy in atherosclerosis obliterans. |