BACKGROUND We aimed to identify the key proteins of miR-142-3p that regulate ferroptosis and ultimately control the downstream effectors of cardiomyocyte growth.AIM To investigate the role of miR-142-3p in regulating ...BACKGROUND We aimed to identify the key proteins of miR-142-3p that regulate ferroptosis and ultimately control the downstream effectors of cardiomyocyte growth.AIM To investigate the role of miR-142-3p in regulating ferroptosis and its impact on diabetes-induced myocardial infarction via the PI3K/AKT/GSK3βpathway.METHODS We constructed bones mesenchymal stem cells(BMCs)with low miR-142-3p expression and investigated its role using cell flow cytometry and western blotting(WB).A diabetes myocardial infarction model was established using streptozotocin and coronary artery ligation.The rats were divided into six groups(n=15 per group):Control,sham surgery model,liraglutide intervention,BMCs intervention,and low miR-142-3p BMCs intervention.Interventions lasted for 7 days and BMCs injected for once.Blood glucose levels were monitored,and myocardial infarction improvements were assessed via electrocardiogra,general heart observation,staining techniques,and WB analysis.RESULTS We observed that miR-142-3p increased BMC apoptosis and affected AKT and GSK3β.The myocardial infarction drug,liraglutide,BMCs,and miR-142-3p low expression BMCs intervention showed improvement in differing degrees.The liraglutide and BMCs showed significant blood glucose reduction(0.05).BMCs increased the expression of PI3K,AKT,and GSK3,leading to an increase in the myocardial infarction intervention group,liraglutide,and BMCs intervention groups.The low miR-142-3p expression intervention with BMCs group had the lowest PI3K and AKT protein expression.Liraglutide improved ferroptosis markers(increased COX-2,decreased GPX4 and CHCHD6).Low miR-142-3p BMCs increased COX-2,GPX4,and CHCHD6.CCM3 and VEGFR2 expression increased in BMCs and low miR-142-3p groups,promoting myocardial repair,but decreased in the low miR-142-3p groups.CONCLUSION The preliminary results showed that the therapeutic mechanism of BMCs in diabetes myocardial infarction may involve miR-142-3p via the PI3K/AKT/GSK-3βaxis,which jointly inhibits ferroptosis and programmed death.展开更多
基金Supported by Health Commission Project,No.Z2014334Natural Science Foundation of Guangxi Province,China,No.2020GXNSFAA238036.
文摘BACKGROUND We aimed to identify the key proteins of miR-142-3p that regulate ferroptosis and ultimately control the downstream effectors of cardiomyocyte growth.AIM To investigate the role of miR-142-3p in regulating ferroptosis and its impact on diabetes-induced myocardial infarction via the PI3K/AKT/GSK3βpathway.METHODS We constructed bones mesenchymal stem cells(BMCs)with low miR-142-3p expression and investigated its role using cell flow cytometry and western blotting(WB).A diabetes myocardial infarction model was established using streptozotocin and coronary artery ligation.The rats were divided into six groups(n=15 per group):Control,sham surgery model,liraglutide intervention,BMCs intervention,and low miR-142-3p BMCs intervention.Interventions lasted for 7 days and BMCs injected for once.Blood glucose levels were monitored,and myocardial infarction improvements were assessed via electrocardiogra,general heart observation,staining techniques,and WB analysis.RESULTS We observed that miR-142-3p increased BMC apoptosis and affected AKT and GSK3β.The myocardial infarction drug,liraglutide,BMCs,and miR-142-3p low expression BMCs intervention showed improvement in differing degrees.The liraglutide and BMCs showed significant blood glucose reduction(0.05).BMCs increased the expression of PI3K,AKT,and GSK3,leading to an increase in the myocardial infarction intervention group,liraglutide,and BMCs intervention groups.The low miR-142-3p expression intervention with BMCs group had the lowest PI3K and AKT protein expression.Liraglutide improved ferroptosis markers(increased COX-2,decreased GPX4 and CHCHD6).Low miR-142-3p BMCs increased COX-2,GPX4,and CHCHD6.CCM3 and VEGFR2 expression increased in BMCs and low miR-142-3p groups,promoting myocardial repair,but decreased in the low miR-142-3p groups.CONCLUSION The preliminary results showed that the therapeutic mechanism of BMCs in diabetes myocardial infarction may involve miR-142-3p via the PI3K/AKT/GSK-3βaxis,which jointly inhibits ferroptosis and programmed death.
文摘目的探讨长链非编码RNA(long non-coding RNA,LncRNA)牛磺酸上调基因1(taurine up-regulated gene 1,TUG1)对非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞生物学行为的影响及分子机制。方法采用qRT-PCR、Western blot分别检测组织(NSCLC癌组织、癌旁组织)和细胞(人正常气管上皮细胞HBE及NSCLC细胞A549、H2009、H1975)中TUG1、miR-142-5p及PD-L1的表达。将pcDNA-TUG1、si-TUG1、miR-142-5p mimics、si-TUG1+anti-miR-142-5p分别转染于A549,qRT-PCR、Western blot分别检测细胞中TUG1、miR-142-5p及PD-L1表达;CCK-8检测细胞增殖;Transwell检测细胞迁移、侵袭;双荧光素酶基因实验分别检测TUG1和miR-142-5p、miR-142-5p和PD-L1的关系;RNA免疫共沉淀检测miR-142-5p与TUG1的相互作用。结果NSCLC组织中TUG1(2.28±0.23 vs 1.00±0)、PD-L1(0.93±0.11 vs 0.25±0.01)表达高于癌旁组织,miR-142-5p(0.31±0.02 vs 1.00±0)表达低于癌旁组织(P<0.05);与人正常气管上皮细胞HBE比较,NSCLC细胞A549中TUG1(3.21±0.27 vs 1.00±0)、PD-L1(1.12±0.12 vs 0.24±0.01)表达水平最高,miR-142-5p(0.23±0.02 vs 1.00±0)表达水平最低(P<0.05);过表达TUG1促进A549细胞增殖、迁移、侵袭;下调TUG1或上调miR-142-5p表达均对A549细胞增殖、迁移、侵袭能力发挥抑制作用;TUG1负调控miR-142-5p,miR-142-5p负调控PD-L1;下调miR-142-5p减弱了沉默TUG1对A549细胞增殖、迁移及侵袭的抑制作用。结论TUG1在NSCLC组织和细胞中高表达,沉默TUG1通过miR-142-5p/PD-L1轴抑制A549细胞的增殖、迁移与侵袭。
