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

Cell Death and Differentiation
Kun WangPei-Feng Li

Abstract

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.

References

Jun 30, 2005·Journal of Cell Science·Daniel TonderaAnsgar Santel
Nov 30, 2005·Nucleic Acids Research·Caifu ChenKarl J Guegler
Aug 25, 2007·Molecular Cancer·Giovanni LanzaMassimo Negrini
Nov 14, 2007·Molecular and Cellular Biology·Yu-Zhen LiPei-Feng Li
Sep 5, 2008·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·An-Heng LiuXiao-Ming Wang
Sep 6, 2008·The Journal of Biological Chemistry·Wei-Qi TanPei-Feng Li
Nov 7, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pierre LauLynn D Hudson
Mar 1, 2013·Nature·Thomas B HansenJørgen Kjems
Mar 1, 2013·Nature·Sebastian MemczakNikolaus Rajewsky
Sep 10, 2013·Cancer Research·Thomas B HansenChristian K Damgaard
May 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Winston KohStephen R Quake
Jun 11, 2014·The Journal of Molecular Diagnostics : JMD·Morten AndersenEric Santoni-Rugiu
Sep 2, 2014·BioMed Research International·Anna B GiliczeAndrás Falus
Sep 23, 2014·Molecular Cell·Reut Ashwal-FlussSebastian Kadener
Dec 3, 2014·RNA·Yang Wang, Zefeng Wang
Apr 2, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Eleftheria BarlakaAntigone Lazou
Apr 30, 2015·Molecular Cell·Agnieszka Rybak-WolfNikolaus Rajewsky
Jul 15, 2015·Journal of Cardiovascular Pharmacology·Huiying ZhaoChengwen Sun

❮ Previous
Next ❯

Citations

Nov 29, 2017·Genes·Shahnaz Haque, Lorna W Harries
Oct 21, 2018·Journal of Cellular Physiology·M-Ashraf AlteshaXiufen Zheng
Oct 17, 2018·The Journal of Clinical Investigation·Qingqing WeiZheng Dong
Sep 8, 2018·Journal of Cellular Physiology·Junqin ShengJianxun Feng
Nov 10, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Shambhabi ChatterjeeThomas Thum
Jan 30, 2019·International Journal of Molecular Sciences·Lina BadimonGemma Vilahur
Jan 19, 2019·Experimental Biology and Medicine·Xue GongChunyu Zeng
Oct 28, 2019·Chinese Medical Journal·Dong LiXiao-Hua Zhu
Jun 13, 2019·Nature Reviews. Cardiology·Dongchao Lu, Thomas Thum
Mar 7, 2020·Basic Research in Cardiology·Amela JusicUNKNOWN EU-CardioRNA COST Action (CA17129)
May 14, 2020·Journal of Cardiovascular Pharmacology·Raj KishoreCarolina Gonzalez
Aug 16, 2017·Scandinavian Journal of Gastroenterology·Penghui Wang, Xiaodong He
May 16, 2020·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Lei ZhangChuan-Shi Xiao
Nov 8, 2018·International Journal of Molecular Sciences·Simona GrecoFabio Martelli
Aug 15, 2019·Cell Death & Disease·Xuebang ZhangYuxia Duan
Jul 25, 2019·Cardiovascular Drugs and Therapy·Vince SiebertYochai Birnbaum
Jan 16, 2020·International Journal of Molecular Sciences·André F GabrielFrancisco J Enguita
Jan 22, 2020·Journal of Cellular Physiology·Xiaolin LiuFengxiang Zhang
Mar 10, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Fei LinChao Liu
Mar 3, 2020·Frontiers in Cell and Developmental Biology·Julie MartoneMonica Ballarino
Apr 18, 2020·Frontiers in Immunology·Rou XieXikun Zhou
Jun 20, 2018·Cancer Biomarkers : Section a of Disease Markers·Jian ZhouWeiwei Tang
Jan 7, 2019·Respiratory Research·Jian WangYuanlin Song
Sep 28, 2018·Current Cardiology Reports·Yao Wei Lu, Da-Zhi Wang
May 23, 2019·Journal of Cellular Physiology·Jia-Jiang-Hui LiYu-Xiang Yan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis