AIFM1, negatively regulated by miR-145-5p, aggravates hypoxia-induced cardiomyocyte injury

• Published in: Biomedical Journal 2022-12, Vol.45 (6), p.870-882
• Main Authors: Zhou, Wugang, Ji, Lv, Liu, Xuqin, Tu, Dan, Shi, Ningning, Yangqu, Wangmu, Chen, Shi, Gao, Pingjin, Zhu, Hong, Ruan, Chengchao
• Format: Article
• Language: English
• Subjects: AIFM1; Animals; Apoptosis - physiology; Apoptosis Inducing Factor - metabolism; Caspase 3 - metabolism; Cell Hypoxia - genetics; Hypoxia - metabolism; Hypoxia - pathology; Hypoxia-induced cardiomyocyte injury; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; miR-145-5p; Myocardial infarction; Myocardial Infarction - genetics; Myocardial Infarction - pathology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Original
• ISSN: 2319-4170; 2320-2890
• DOI: 10.1016/j.bj.2021.11.012

Hypoxia-induced apoptosis is linked to the pathogenesis of myocardial infarction. The role of apoptosis-inducing factor mitochondria associated 1 (AIFM1) in cardiomyocyte injury remains unclear. This study was aimed at probing into the role and the underlying regulatory mechanism of AIFM1 in myocardial injury. H9c2 cardiomyocytes and C57BL/6 mice were used for myocardial hypoxic/ischemic injury and myocardial infarction animal models. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the expression levels of AIFM1 mRNA and miR-145-5p. Western blot was used for examining the expression levels of AIFM1, caspase-3, cleaved caspase-3, p-53, and γ-H2AX. Cell viability was examined by cell counting kit-8 (CCK-8) assay and BrdU assay. Interaction between AIFM1 and miR-145-5p was determined by bioinformatics analysis, qRT-PCR, Western blot, and dual-luciferase reporter assay. AIFM1 expression was markedly highly elevated, while miR-145-5p expression was significantly down-regulated in the myocardial infarction animal model and H9c2 cells under hypoxia. Augmentation of AIFM1 led to a dramatic decrease of cell viability, accompanied by an increase of the secretion of the inflammatory cytokines IL-1β, TNF-α, IL-6, and the expression of cleaved caspase-3. Furthermore, AIFM1 was identified as a target of miR-145-5p. In addition, miR-145-5p/AIFM1 axis regulated the expression of p53. AIFM1 may exacerbate myocardial ischemic injury by promoting inflammation and the injury of cardiomyocytes, and its up-regulation may be partly due to the down-regulation of miR-145-5p.