Dysregulation of the miR-1275/HK2 Axis Contributes to the Progression of Hypoxia/Reoxygenation-Induced Myocardial Injury

• Published in: Archives of medical research 2021-07, Vol.52 (5), p.461-470
• Main Authors: Tong, Qin-Hong, Hu, Hai-Ying, Chai, Hui, Wu, Ai-Bin, Guo, Xiao-Hu, Wang, Shan, Zhang, Yu-Feng, Fan, Xiao-Yong
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell Hypoxia; Cell Line; Heart Failure - genetics; Heart Failure - physiopathology; HK2; Humans; Hypoxia - metabolism; Hypoxia/reoxygenation; Inflammatory; MicroRNAs - genetics; MicroRNAs - metabolism; miR-1275; Myocytes, Cardiac - metabolism
• ISSN: 0188-4409; 1873-5487
• DOI: 10.1016/j.arcmed.2021.01.006

This research was designed to investigate the function of miR-1275 in hypoxia/reoxygenation (H/R)-induced myocardial injury and its in-depth mechanism. Firstly, the differential expression of miR-1275 in patients with heart failure and healthy control were analyzed based on Gene Expression Omnibus (GEO) database. Then H/R model was constructed in vitro with AC16 cells. The qRT-PCR assay was performed to analyze the expression of miR-1275 in H/R-treated cells. Afterwards, CCK-8 assay and flow cytometry assay were carried out to detect the cells viability and apoptosis. Bioinformatics prediction, western blotting and dual-luciferase reporter assays were set to check the target gene of miR-1275. Finally, we used an Elisa to test the effect of miR-1275/HK2 axis on inflammatory factors. We found that miR-1275 was highly expressed in patients with heart failure and H/R treated AC16 cells than that in control group, and inhibition of miR-1275 can alleviate induced-decrease of cell viability. Subsequently, we revealed that HK2 was a downstream target gene of miR-1275, which was lowly expressed in patients with heart failure. Furthermore, our data also suggested that inhibition of miR-1275 can significantly alleviate H/R-induced myocardial injury, which can also markedly decrease the concentration of pro-inflammatory factors TNF-α, IL-1 β and increase the concentration of anti-inflammatory factors IL-10 in H/R-treated AC16 cells, while knockdown of HK2 canceled the effect caused by miR-1275 deletion. In summing, our results illustrated that miR-1275/HK2 axis act as a potential regulator to against H/R-induced AC16 cells injury through anti-inflammatory effect.