PMID- 35547044 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230916 IS - 2046-2069 (Electronic) IS - 2046-2069 (Linking) VI - 8 IP - 61 DP - 2018 Oct 10 TI - miR-183-96-182 clusters alleviated ox-LDL-induced vascular endothelial cell apoptosis in vitro by targeting FOXO1. PG - 35031-35041 LID - 10.1039/c8ra06866f [doi] AB - OBJECTIVE: To investigate the role of FOXO1 and miR-183-96-182 clusters in ox-LDL induced endothelial cell apoptosis. METHODS: FOXO1 overexpression (OE) and knockdown (KD) as well as AKT1 OE in human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs) were achieved by lentiviral transduction. Upregulation of miR-183-5p, miR-182-5p or miR-96-5p was mimicked by agomir treatment. FOXO1 gene transcription was monitored by FOXO1 promotor reporter assay. Cell apoptosis in culture was monitored by TiterTACS in situ detection. Regulation of FOXO1 gene expression by an miRNA targeting mechanism was monitored by AGO2-RNA immunoprecipitation assay. RESULTS: FOXO1 mRNA and protein expression levels in ox-LDL treated HUVECs or HAECs were significantly upregulated due to transcriptional and miRNA targeting mechanisms. MiR-183-5p, miR-182-5p and miR-96-5p expression levels in HUVECs or HAECs were significantly reduced by ox-LDL treatment, the overexpression of which by agomir treatment partially reduced the FOXO1 mRNA/protein expression levels and cell apoptosis which was upregulated by ox-LDL treatment. FOXO1 overexpression antagonized the effect of the agomir treatment indicated above. MiR-183-5p, miR-182-5p and miR-96-5p agomir treatment partially rescued the FOXO1 pSer256/total FOXO1 protein ratio and the AKT1 pSer473 level that were reduced by ox-LDL treatment in the HUVECs or HAECs. AKT1 overexpression significantly reduced FOXO1 protein expression, increased miR-182-5p and miR-183-5p expression, and partially alleviated ox-LDL induced HUVEC or HAEC apoptosis in an miR-183-5p and miR-182-5p-dependent manner. CONCLUSION: miR-183-96-182 clusters could partially alleviate ox-LDL-induced apoptosis in HUVECs or HAECs by targeting FOXO1. CI - This journal is (c) The Royal Society of Chemistry. FAU - Liu, Zhi-Qin AU - Liu ZQ AD - Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University, School of Medicine Xi'an 710003 Shaanxi China. FAU - Du, Jing-Jing AU - Du JJ AD - Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University, School of Medicine Xi'an 710003 Shaanxi China. FAU - Ren, Jing-Jing AU - Ren JJ AD - Department of Hematology, Xi'an Central Hospital, Xi'an Jiaotong University, School of Medicine Xi'an 710003 Shaanxi China. FAU - Zhang, Zhi-Yong AU - Zhang ZY AD - Department of Neurology, China-Japan Friendship Hospital Beijing 100029 China. FAU - Guo, Xiao-Bo AU - Guo XB AD - Department of Hematology, Xi'an Central Hospital, Xi'an Jiaotong University, School of Medicine Xi'an 710003 Shaanxi China. FAU - Yan, Yu-E AU - Yan YE AD - Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University, School of Medicine Xi'an 710003 Shaanxi China. FAU - Jia, Xiao-Tao AU - Jia XT AD - Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University, School of Medicine Xi'an 710003 Shaanxi China. FAU - Gu, Nai-Bing AU - Gu NB AD - Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University, School of Medicine Xi'an 710003 Shaanxi China. FAU - Di, Zheng-Li AU - Di ZL AD - Department of Neurology, Xi'an Central Hospital, Xi'an Jiaotong University, School of Medicine Xi'an 710003 Shaanxi China. FAU - Li, San-Zhong AU - Li SZ AUID- ORCID: 0000-0002-7570-6310 AD - Department of Neurosurgery, Xi-jing Hospital Fourth Military Medical University No. 127, Changle Xi Road Xi'an 710032 Shaanxi China lzqsjnk@126.com +86-185-9140-9510. LA - eng PT - Journal Article DEP - 20181012 PL - England TA - RSC Adv JT - RSC advances JID - 101581657 PMC - PMC9087689 COIS- The authors declare that there are no conflicts of interest. EDAT- 2018/10/12 00:00 MHDA- 2018/10/12 00:01 PMCR- 2018/10/12 CRDT- 2022/05/13 11:08 PHST- 2018/08/16 00:00 [received] PHST- 2018/09/17 00:00 [accepted] PHST- 2022/05/13 11:08 [entrez] PHST- 2018/10/12 00:00 [pubmed] PHST- 2018/10/12 00:01 [medline] PHST- 2018/10/12 00:00 [pmc-release] AID - c8ra06866f [pii] AID - 10.1039/c8ra06866f [doi] PST - epublish SO - RSC Adv. 2018 Oct 12;8(61):35031-35041. doi: 10.1039/c8ra06866f. eCollection 2018 Oct 10.