The role of miR-711 in cardiac cells in response to oxidative stress and its biogenesis: a study on H9C2 cells

Cellular & Molecular Biology Letters

Kexiang Liu¹  Cuilin Zhu¹  Duo Zhao¹  Hao Zheng²  Adam Greasley²  Bowen Wang²  Tiffany Ni²  Ishita Topiwala²  Fengjun Ling²  Xiufen Zheng²  Qinfeng Zhou²  Tina Mele³ 

[1] Department of Cardiovascular Surgery, The Second Hospital of Jilin University;Department of Pathology and Laboratory Medicine, Western University;Department of Surgery, Western University;

关键词: miR-711;    Oxidative stress;    HIF-1α;    NFКB;    Ang-1;    FGF14;   

DOI  :  10.1186/s11658-020-00206-z

来源: DOAJ

【 摘 要 】

Abstract Background Oxidative stress results in cell apoptosis/death and plays a detrimental role in disease development and progression. Stressors alter the miRNA expression profile and miRNAs play a role in the cell response to stress. We previously showed that miR-711 is significantly over-expressed in extended cold ischemia reperfusion injured hearts in heart transplant. In this study, we aimed to investigate the role of miR-711 in cardiac cell damage in response to oxidative stress and how miR-711 is regulated. Methods Rat cardiac cell line H9c2 cells were cultured and exposed to oxidative conditions (Antimycin A (AA), H2O2, CoCl2, or cold hypoxia/reoxygenation (H/R)) in vitro. H9c2 cells were transfected with miR-711 mimics, miR-711 inhibitors, or small interference RNA, using transfection reagents. The expression of miR-711 was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell apoptosis/death was detected by flow cytometry and an IncuCyte system. Mitochondrial damage was detected by measuring the mitochondria membrane potential by flow cytometry. Gene expression was detected by qRT-PCR at the mRNA level and Western blotting and immunocytochemistry staining at the protein level. Results We found that miR-711 was significantly up-regulated in cells treated with H2O2, AA, CoCl2, and cold H/R. Over-expression of miR-711 increased cell apoptosis/death induced by AA and H/R whereas cell death was reduced by miR-711 inhibitors. MiR-711 induced cell death through negative regulation of angiopoietin 1 (Ang-1), fibroblast growth factor 14 (FGF14) and calcium voltage-gated channel subunit alpha1C (Cacna1c) genes. Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. Conclusion Oxidative stress increases the expression of miR-711. Over-expression of miR-711 induces cell apoptosis/death. HIF-1α and NFКB regulate miR-711 in H9c2 cells during oxidative stress. miR-711 is a new target for preventing oxidative stress.

【 授权许可】

Unknown