An experimental study on the effect of CircFoxo3 regulating miR-130a-5p/TEAD1 axis on myocardial cell apoptosis in heart failure rats
CAO Yanhua
LE Jinhai
CHEN Xinyu
LIU Jianhe
LIU Yuemei
LI Jun
LI Su
Abstract：Objective To explore the effect of circular RNA forkhead box protein O3(CircFoxo3)regulating micro ribonucleic acid-130a-5p(miR-130a-5p)/TEA domain transcription factor 1(TEAD1)axis on myocardial cell apoptosis in heart failure(HF)rats.Methods Sprague-Dawley(SD)rats were divided into control group,HF group,si-NC group,si-CircFoxo3 group,agomir NC group,miR-130a-5p agomir group,si-CircFoxo3+antagomir NC group and si-CircFoxo3+miR-130a-5p antagomir group,with 18 rats in each group.Except for the rats in the control group,the rats in the other groups were injected with doxorubicin hydrochloride intraperitoneally to construct HF rat models.After successful modeling,medication was administered once every 3 days for 3 weeks.Quantitative reverse transcrip-tion polymerase chain reaction(qRT-PCR)was applied to detect the expression levels of CircFoxo3 and miR-130a-5p in the myocardial tissues.Color Doppler ultrasound was applied to detect the levels of left ventricular end systolic diam-eter(LVESD),left ventricular end diastolic diameter(LVEDD),and left ventricular ejection fraction(LVEF)in the rats.Enzyme-linked immunosorbent assay(ELISA)method was applied to detect the levels of human stromelysin-2(ST2)and N-terminal pro-brain natriuretic peptide(NT-pro BNP)in the serum of the rats.Haematoxylin-eosin(HE)staining and Masson staining were used to detect the pathological changes and the myocardial fibrosis in the myocardial tissues of the rats.TUNEL staining was applied to detect the level of cardiomyocyte apoptosis.Western blot method was applied to detect the expression levels of TEAD1,B cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and cleaved aspartate-specific cysteine protease-3(cleaved caspase-3)in the myocardial tissues of the rats.Double luciferase reporter gene experiment was applied to verify the relationship between CircFoxo3 and miR-130a-5p,and between miR-130a-5p and TEAD1.Results Compared with those in the control group,the rats in the HF group had pathological injury of myo-cardial tissues and severe myocardial fibrosis,elevated levels of LVESD and LVEDD,elevated levels of CircFoxo3,TEAD1,Bax and cleaved caspase-3 protein expressions in the myocardial tissues,elevated levels of ST2 and NT-pro BNP in the serum,elevated cardiomyocyte apoptosis rate,and decreased levels of LVEF,miR-130a-5p and Bcl-2 protein,and the differences were significant(P＜0.05).Compared with those in the HF group and the si-NC group,the rats in the si-CircFoxo3 group had mitigated pathological injury of myocardial tissues,decreased levels of LVESD and LVEDD,decreased expression levels of CircFoxo3,TEAD1,Bax and cleaved caspase-3 protein expression in the myocardial tis-sues,decreased levels of ST2 and NT-pro BNP in the serum,decreased cardiomyocyte apoptosis rate,and elevated levels of LVEF,miR-130a-5p and Bcl-2 protein,and the differences were significant(P＜0.05).Compared with those in the HF group and the agomir NC group,the rats in the miR-130a-5p agomir group had improved pathological injury and myocardial fibrosis in the myocardial tissues,decreased levels of LVESD and LVEDD,decreased levels of TEAD1,Bax,cleaved caspase-3 protein expressions in the myocardial tissues,decreased levels of ST2 and NT-pro BNP in the serum,decreased cardiomyocyte apoptosis rate,and elevated levels of LVEF,miR-130a-5p and Bcl-2 protein,and the differences were significant(P＜0.05).Compared with those in the si-CircFoxo3 group and the si-CircFoxo3+antagomir NC group,the rats in the si-CircFoxo3+miR-130a-5p antagomir group had aggravated pathological injury and myocardial fibrosis in the myocardial tissues,elevated levels of LVESD and LVEDD,elevated levels of TEAD1,Bax,cleaved caspase-3 protein expressions in the myocardial tissues,elevated levels of ST2 and NT-pro BNP in the serum,elevated cardiomyocyte apoptosis rate,and decreased levels of LVEF,miR-130a-5p and Bcl-2 protein,and the differ-ences were significant(P＜0.05).CircFoxo3 had a targeted relationship with miR-130a-5p,and miR-130a-5p had a targeted relationship with TEAD1.Conclusion Silencing CircFoxo3 may inhibit the expression of TEAD1 via sponging miR-130a-5p upwards,thereby inhibiting cardiomyocyte apoptosis in HF rats.
Keywords：Circular RNA forkhead box protein O3(CircFoxo3)Micro ribonucleic acid-130a-5p(miR-130a-5p)TEA domain transcription factor 1(TEAD1)Heart failure(HF)Apoptosis
Publication Date：2024-01-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 65-73 )