Omega-3 fatty acid protects cardiomyocytes against hypoxia-induced injury through targeting MiR-210-3p/CASP8AP2 axis

• Published in: Molecular and cellular biochemistry 2021-08, Vol.476 (8), p.2999-3007
• Main Authors: Yu, Xueju, Liu, Fengyao, Liu, Yuting, Bai, Bingqing, Yin, Han, Wang, Haochen, Feng, Yingqing, Ma, Huan, Geng, Qingshan
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cardiology; Cardiomyocytes; Caspase-8; Docosahexaenoic acid; Fatty acids; Flow cytometry; Gene expression; Gene regulation; Genetic transcription; Heart cells; Hypoxia; Immunoblotting; Life Sciences; Medical Biochemistry; MicroRNA; MicroRNAs; miRNA; Omega-3 fatty acids; Oncology; Post-transcription; Proteins; Ribonucleic acid; RNA; Signal transduction; siRNA; Supplements; Unsaturated fatty acids
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-021-04141-1

MicroRNAs (miRs) regulate diverse biological functions in both normal and pathological cellular conditions by post-transcriptional regulation of various genes expression. Nevertheless, the role of miRs in regulating the protective functions of omega-3 fatty acid in relation to hypoxia in cardiomyocytes remains unknown. The aim of this study was to investigate the effects of omega-3 fatty acid supplementation on cardiomyocyte apoptosis and further delineate the mechanisms underlying microRNA-210 (miRNA-210)-induced cardiomyocyte apoptosis in vitro. H9C2 cultured cells were first subjected to hypoxia followed by a subsequent treatment with main component of the Omega-3 fatty acid, Docosahexaenoic Acid (DHA). Cell apoptosis were detected by flow cytometry and the expression of miR-210-3p were detected by RT-qPCR and caspase-8-associated protein 2 (CASP8AP2) at protein levels by immunoblotting. Dual luciferase assay was used to verify the mutual effect between miR-210-3p and the 3′-untranslated region (UTR) of CASP8AP2 gene. DHA was shown to reduce apoptosis in H9C2 cells subjected to hypoxia. While DHA caused a significant increase in the expression of miR-210-3p, there was a marked reduction in the protein expression of CASP8AP2. MiR-210-3p and CASP8AP2 were significantly increased in H9C2 cardiomyocyte subjected to hypoxia. Overexpression of miR-210-3p could ameliorate hypoxia-induced apoptosis in H9C2 cells. MiR-210-3p negatively regulated CASP8AP2 expression at the transcriptional level. Both miR-210-3p mimic and CASP8AP2 siRNA could efficiently inhibit apoptosis in H9C2 cardiomyocyte subjected to hypoxia. We provide strong evidence showing that Omega-3 fatty acids can attenuate apoptosis in cardiomyocyte under hypoxic conditions via the up-regulation of miR-210-3p and targeting CASP8AP2 signaling pathway.