Research Paper Volume 13, Issue 7 pp 10158—10174
Hypoxia-induced miR-27 and miR-195 regulate ATP consumption, viability, and metabolism of rat cardiomyocytes by targeting PPARγ and FASN expression
- 1 ICU, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong, China
- 2 ICU, People’s Hospital of Tajik Autonomous County, Tashkurgan, Xinjiang Uygur Autonomous Region, China
- 3 Respiratory Department, The First People’s Hospital of Kashgar Region, Xinjiang Uygur Autonomous Region, China
- 4 Department of Internal Medicine, People’s Hospital of Tajik Autonomous County, Tashkurgan, Xinjiang Uygur Autonomous Region, China
- 5 Emergency Department, Shenzhen Hospital of University of Hong Kong, Shenzhen, Guangdong, China
- 6 People’s Hospital of Tajik Autonomous County, Tashkurgan, Xinjiang Uygur Autonomous Region, China
- 7 Department of Cardiology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, China
- 8 Department of Cardiovascular Medicine, Fuwai Hospital, Chinese Academy of Medical Science, Shenzhen, Guangdong, China
Received: August 24, 2020 Accepted: February 16, 2021 Published: March 26, 2021https://doi.org/10.18632/aging.202778
How to Cite
Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This study examined whether hypoxia-induced microRNA (miRNA) upregulation was related to the inhibition of chondriosome aliphatic acid oxidation in myocardial cells under anoxia. We showed that anoxia induced high expression of hypoxia-inducible factor-1-alpha, muscle carnitine palmitoyltransferase I, and vascular endothelial growth factor in cardiomyocytes. Meanwhile, miR-27 and miR-195 were also upregulated in hypoxia-induced cardiomyocytes. Furthermore, hypoxia induction led to reductions in the adenosine triphosphate (ATP) consumption rate and oxidative metabolism as well as an increase in cardiomyocyte glycolysis. Metabolic reprogramming was reduced by hypoxia, as evidenced by the downregulation of sirtuin 1, forkhead box protein O1, sterol regulatory element-binding protein 1c, ATP citrate lyase, acetyl-coenzyme A carboxylase 2, adiponutrin, adipose triglyceride lipase, and glucose transporter type 4, while miR-27 and miR-195 inhibition partially recovered the expression of these transcription factors. In addition, hypoxia induction reduced cell viability and survival by triggering apoptosis; however, miR-27 and miR-195 inhibition partially increased cell viability. Moreover, miR-27 and miR-195 targeted the 3’untranslated regions of two key lipid-associated metabolic players, peroxisome proliferator-activated receptor gamma and fatty acid synthase. In conclusion, miR-27 and miR-195 are related to hypoxia-mediated ATP levels, glycolysis, oxidation, cell survival, and a cascade of transcription factors that control metabolism in cardiomyocytes.
miRNA or miR: microRNA; mCPT-I: muscle carnitine palmitoyltransferase I; LM: lipid metabolism; MR: metabolic reprogramming; PH: pulmonary hypertension; MS: metabolic syndrome; FASN: fatty acid synthase; NC: negative control; RT-qPCR: real-time quantitative polymerase chain reaction; WB: western blotting; PI: propidium iodide; DLRA: dual-luciferase reporter assay; WT: wild type; MU: mutant; SREBP1c: sterol regulatory element-binding transcriptional factor 1; ACACB: acetyl-CoA carboxylase; ACLY: ATP-citrate lyase; ADPN: adiponutrin; ATGL: adipose triglyceride lipase; HF: heart failure.