PMID- 37967592 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240405 IS - 1873-6815 (Electronic) IS - 0531-5565 (Linking) VI - 184 DP - 2023 Dec TI - MiR-20b-5p involves in vascular aging induced by hyperhomocysteinemia. PG - 112330 LID - S0531-5565(23)00251-6 [pii] LID - 10.1016/j.exger.2023.112330 [doi] AB - Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis (AS). Some reports have shown that homocysteine (Hcy) could accelerate the development of AS by promoting endothelial cell senescence. miRNAs were widely involved in the pathophysiology of HHcy. However, few studies have focused on the changes of miRNA-mRNA networks in the artery of HHcy patients. For this reason, RNA-sequencing was adopted to investigate the expression of miRNA and mRNA in HHcy model mouse arteries. We found that the expression of 216 mRNAs and 48 miRNAs were significantly changed. Using TargetScan and miRDB web tools, 29 miRNA-mRNA pairs were predicted. Notably, miR-20b-5p and FJX1 shared the highest predicted score in TargetScan, and further study indicated that the miR-20b-5p inhibitor significantly upregulated the FJX1 expression in HHcy human umbilical vein endothelial cells (HUVECs) model. PPI analysis revealed an important sub-network which was centered on CDK1. Gene ontology (GO) enrichment analysis showed that HHcy had a significant effect on cell cycle. Further experiments found that Hcy management increased reactive oxygen species (ROS) generation, the activity of senescence associated beta-galactosidase (SA-beta-gal) and the protein expression of p16 and p21 in HUVECs, which were rescued by miR-20b-5p inhibitor. In general, our research indicated the important role of miR-20b-5p in HHcy-related endothelial cell senescence. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Qin, Hao AU - Qin H AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. FAU - Hu, Long-Long AU - Hu LL AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. FAU - Wang, Wen-Jun AU - Wang WJ AD - Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. FAU - Yu, Zuo-Zhong AU - Yu ZZ AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. FAU - Chen, Yang AU - Chen Y AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. FAU - Zhao, Yuan-Bin AU - Zhao YB AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. FAU - Liao, Yan-Hui AU - Liao YH AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. FAU - Zhang, Wei-Lin AU - Zhang WL AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. FAU - Yang, Ren-Qiang AU - Yang RQ AD - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China. Electronic address: Yang.RQ@ncu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231116 PL - England TA - Exp Gerontol JT - Experimental gerontology JID - 0047061 RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Mice MH - *Atherosclerosis/genetics MH - Cellular Senescence/genetics MH - Human Umbilical Vein Endothelial Cells MH - *Hyperhomocysteinemia/genetics MH - *MicroRNAs/genetics/metabolism MH - RNA, Messenger/metabolism OTO - NOTNLM OT - Atherosclerosis (AS) OT - FJX1 OT - Hyperhomocysteinemia (HHcy) OT - Senescence OT - miR-20b-5p COIS- Declaration of competing interest The authors declare no conflicts of interest regarding this work. The corresponding authors have the right to and do speak on behalf of all authors. EDAT- 2023/11/16 00:42 MHDA- 2023/12/17 13:19 CRDT- 2023/11/15 19:20 PHST- 2023/10/18 00:00 [received] PHST- 2023/11/09 00:00 [revised] PHST- 2023/11/12 00:00 [accepted] PHST- 2023/12/17 13:19 [medline] PHST- 2023/11/16 00:42 [pubmed] PHST- 2023/11/15 19:20 [entrez] AID - S0531-5565(23)00251-6 [pii] AID - 10.1016/j.exger.2023.112330 [doi] PST - ppublish SO - Exp Gerontol. 2023 Dec;184:112330. doi: 10.1016/j.exger.2023.112330. Epub 2023 Nov 16.