Hypoxia-induced miR-27 and miR-195 regulate ATP consumption, viability, and metabolism of rat cardiomyocytes by targeting PPARγ and FASN expression

Abstract

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.

Baicalein inhibits macrophage lipid accumulation and inflammatory response by activating the PPARγ/LXRα pathway

“…On the other hand, we do not clarify how baicalein up-regulates PPARγ expression. Several lines of evidence have identified PPARγ as a direct target of miR-27 [ 48 , 49 ]. Baicalein serves as a regulator of many miRNAs [ 50 , 51 ].…”

Identification and Functional Verification Reveals that miR-195 Inhibiting THRSP to Affect Fat Deposition in Xinyang Buffalo

“…It has been reported that the ectopic expression of miR-195 suppresses the expression of INSR , thereby impairing the insulin signaling cascade and glycogen synthesis in HepG2 cells ( Yang et al, 2014 ). Meanwhile, miR-195 is able to target FNAS to regulate ATP consumption and cell migration ( Mao et al, 2012 ; Lin et al, 2021 ). This suggests that the same miRNA will serve different functions depending on the target genes.…”

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

“…169 Studies have suggested that miR-27 and miR-195 are also upregulated in hypoxia-induced cardiomyocytes, suppressing the expression of ACLY and ACC. 170,171 The mechanism of ACLY regulation in tumor cells under hypoxic conditions is still unclear. ACC (including ACC1 and ACC2) is the rate-limiting enzyme in the FA synthesis pathway.…”