广西医科大学学报2025，Vol.42Issue(3)：342-350,9.DOI:10.16190/j.cnki.45-1211/r.2025.03.003
Hsa-miR-146b-3p靶向CREB3L3调控PI3K/Akt通路促进内皮细胞功能障碍及动脉粥样硬化进程
Hsa-miR-146b-3p promotes endothelial cell dysfunction and atherosclerosis development by targeting CREB3L3 to regulate the PI3K/Akt signaling pathway
摘要
Abstract
Objective:To explore the effects of hsa-miR-146b-3p on endothelial cells and the possible roles and mechanisms of hsa-miR-146b-3p in the development of atherosclerosis.Methods:Lentivirus was used to con-struct an endothelial cell intervention model in EA.hy926 cells.The cells were categorized into two distinct groups:overexpression groups,including the OE_hsa-miR-146b-3p group and the OE_control group;and silenc-ing groups,consisting of the SH_hsa-miR-146b-3p group and the SH_control group.The cell counting kit-8(CCK-8)assay was used to detect the proliferation ability of cells,while scratching and Transwell assays were employed to assess the migration ability.Cell cycle and apoptosis assays were respectively conducted to explore the distribution characteristics and apoptosis rate of cells.The downstream targets of hsa-miR-146b-3p were veri-fied by RNA sequencing(RNA-seq)and dual-luciferase assay.Finally,the expression levels of target genes were detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and western blotting.Re-sults:Compared with the control group,overexpression of hsa-miR-146b-3p significantly promoted the prolifera-tion(P＜0.01),migration(P＜0.0001)of EA.hy926 cells and the cell proportion in the S phase(P＜0.01),and in-creased the late apoptosis rate and total apoptosis rate(P＜0.05).The silencing groups showed inhibited prolifera-tion(P＜0.05),weakened migration(P＜0.0001),a decreased proportion of cells in the S phase(P＜0.05),and reduced early-stage apoptosis(P＜0.05).RNA-seq combined with dual-luciferase assay confirmed that hsa-miR-146b-3p regulated CREB3L3 via the PI3K/Akt pathway(P＜0.001).RT-qPCR and western blotting results showed that overexpression of hsa-miR-146b-3p led to a decrease in CREB3L3 expression level.Conclusion:Hsa-miR-146b-3p may influence the function of endothelial cells and promote the development of atherosclerosis by downregulating the expression level of the CREB3L3 gene and the PI3K/Akt pathway.关键词
hsa-miR-146b-3p/冠心病/转录组测序/PI3K/Akt信号通路Key words
hsa-miR-146b-3p/coronary heart disease/RNA sequencing/PI3K/Akt signaling pathway分类
医药卫生引用本文复制引用
周世繁,张书铭,陈宁园,黄玲,宋重阳,潘尚领,彭均华..Hsa-miR-146b-3p靶向CREB3L3调控PI3K/Akt通路促进内皮细胞功能障碍及动脉粥样硬化进程[J].广西医科大学学报,2025,42(3):342-350,9.基金项目
国家自然科学基金地区项目(No.32060188) （No.32060188）
