Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of MTP18 expression

Circular RNAs (circRNAs) have important roles in several cellular processes. No study has established the pathophysiological role for circRNAs in the heart. Here, we show that a circRNA (mitochondrial fission and apoptosis-related circRNA (MFACR)) regulates mitochondrial fission and apoptosis in the...

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Bibliographic Details
Published in:Cell death and differentiation 2017-06, Vol.24 (6), p.1111-1120
Main Authors: Wang, Kun, Gan, Tian-Yi, Li, Na, Liu, Cui-Yun, Zhou, Lu-Yu, Gao, Jin-Ning, Chen, Chao, Yan, Kao-Wen, Ponnusamy, Murugavel, Zhang, Yu-Hui, Li, Pei-Feng
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biomarkers
Cancer
Cardiomyocytes
Cardiovascular disease
Cell death
Gene Expression Regulation
Heart
Heart failure
Medicine
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
MicroRNAs
MicroRNAs - metabolism
Mitochondria
Mitochondria - metabolism
Mitochondria - physiology
Mitochondrial Dynamics
Myocardial Infarction - metabolism
Myocardial Infarction - physiopathology
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - physiology
Original Paper
RNA - metabolism
Signal Transduction
Tumor Suppressor Proteins - metabolism
Up-Regulation
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Summary:Circular RNAs (circRNAs) have important roles in several cellular processes. No study has established the pathophysiological role for circRNAs in the heart. Here, we show that a circRNA (mitochondrial fission and apoptosis-related circRNA (MFACR)) regulates mitochondrial fission and apoptosis in the heart by directly targeting and downregulating miR-652-3p; this in turn blocks mitochondrial fission and cardiomyocyte cell death by suppressing MTP18 translation. MTP18 deficiency reduces mitochondrial fission and suppresses cardiomyocyte apoptosis and MI. miR-652-3p directly downregulates MTP18 and attenuates mitochondrial fission, cardiomyocyte apoptosis, and MI in vitro and in vivo. MFACR directly sequesters miR-652-3p in the cytoplasm and inhibits its activity. MFACR knockdown in cardiomyocytes and mice attenuates mitochondrial fission and MI. Our results reveal a crucial role for circRNA in regulating mitochondrial dynamics and apoptosis in the heart; as such, circRNAs may serve as a potential therapeutic avenue for cardiovascular diseases.
ISSN:1350-9047
1476-5403
DOI:10.1038/cdd.2017.61