首页|Functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure

Functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure

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Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure,with noncoding RNAs exerting regulatory influence.However,the molecular function of circular RNAs(circRNAs)in the progression from cardiac hypertrophy to heart failure remains unclear.To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure,we construct a global triple network(microRNA,circRNA,and mRNA)based on the competitive endogenous RNA(ceRNA)theory.We observe that cardiac hypertrophy-related circRNA(circRNA CHRC),within the ceRNA network,is down-regulated in both transverse aortic constriction mice and Ang-Ⅱ-treated primary mouse cardiomyocytes.Silencing circRNA CHRC increases cross-sectional cell area,atrial natriuretic peptide,and β-myosin heavy chain levels in primary mouse cardiomyocytes.Further screening shows that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro.Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p,while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC over-expression.In summary,circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

circRNA CHRCHeart failureceRNAmiR-431-4pKlf15

Yi Hu、Huaming Cao、Jie Sheng、Yizhuo Sun、Yuping Zhu、Qin Lin、Na Yi、Siyu He、Luying Peng、Li Li

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State Key Laboratory of Cardiology and Medical Innovation Center,Shanghai East Hospital,Tongji University School of Medicine,Shanghai 200120,China

Shanghai Arrhythmias Research Center,Shanghai East Hospital,Tongji University School of Medicine,Shanghai 200120,China

Laboratory of Molecular Genetics and Stem Cell Differentiation,Tongji University School of Medicine,Shanghai 200120,China

Department of Cardiology,Shanghai Shibei Hospital,Shanghai 200435,China

Research Units of Origin and Regulation of Heart Rhythm,Chinese Academy of Medical Sciences,Shanghai 200120,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaShanghai Committee of Science and TechnologyShanghai Committee of Science and TechnologyShanghai Jing'an District Discipline Construction ProjectCAMS Innovation Fund for Medical SciencesLi Li is a fellow at the Collaborative Innovation Center For Cardiovascular Disease Translational Medicine,Nanjing Medical Unive

3207110982070270M-004822ZR146380021ZR14670002021PY032019-I2M-5-053

2024

10.1016/j.jgg.2024.03.010

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(8)