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

Abstract

Objective: This research was designed to investigate the function of miR-1275 in hypoxia/reoxygenation (H/R)-induced myocardial injury and its in-depth mechanism.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: HK2; Hypoxia/reoxygenation; Inflammatory; miR-1275.