遗传学报2024，Vol.51Issue(8) ：844-854.DOI:10.1016/j.jgg.2024.03.010

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

Yi Hu Huaming Cao Jie Sheng Yizhuo Sun Yuping Zhu Qin Lin Na Yi Siyu He Luying Peng Li Li
遗传学报2024，Vol.51Issue(8) ：844-854.DOI:10.1016/j.jgg.2024.03.010
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Functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure

Yi Hu 1Huaming Cao 2Jie Sheng 1Yizhuo Sun 1Yuping Zhu 1Qin Lin 1Na Yi 1Siyu He 1Luying Peng 3Li Li3
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作者信息

  • 1. 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
  • 2. Department of Cardiology,Shanghai Shibei Hospital,Shanghai 200435,China
  • 3. 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;Research Units of Origin and Regulation of Heart Rhythm,Chinese Academy of Medical Sciences,Shanghai 200120,China
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Abstract

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.

Key words

circRNA CHRC/Heart failure/ceRNA/miR-431-4p/Klf15

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基金项目

National Natural Science Foundation of China(32071109)

National Natural Science Foundation of China(82070270)

National Natural Science Foundation of China(M-0048)

Shanghai Committee of Science and Technology(22ZR1463800)

Shanghai Committee of Science and Technology(21ZR1467000)

Shanghai Jing'an District Discipline Construction Project(2021PY03)

CAMS Innovation Fund for Medical Sciences(2019-I2M-5-053)

Li Li is a fellow at the Collaborative Innovation Center For Cardiovascular Disease Translational Medicine,Nanjing Medical Unive()

出版年

2024
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
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