Objective: Arsenic trioxide (As2O3) an evident effect in the treatment of acute promyelocytic leukemia and other malignant tumors in recent years. However, more and more studies have found that the cardiac toxicity of As2O3 was increased, limiting its wide clinical application. This study aims to explore the molecule mechanisms of As2O3 on cardiomyocyte injury.
Materials and methods: The cardiomyocyte injury under As2O3 was detected by MTT assay. The levels of NEAT1 and miR-124 were examined by RT-PCR. The functions of NEAT1 and miR-124 at H9c2 cell injury under As2O3 were detected by cell transfection of the overexpression or repression. The expression levels of inflammation factors, apoptosis genes and NF-κB signals were measured by Western blot in H9c2 cell lines under As2O3. The luciferase assay detected the direct interaction between NEAT1 and miR-124.
Results: The overexpression of NEAT1 decreased the H9c2 cells injury under As2O3. The levels of IL-1β, IL-6, TNF-α were upregulated after NEAT1 overexpression. Moreover, the luciferase assay results showed NEAT1 was directly interacting with miR-124. Silencing of miR-124 significantly increased the H9c2 cell survival under As2O3 by repressing NF-κB signaling pathway. Furthermore, the overexpression of NEAT1 markedly increased H9c2 cells survival under As2O3, while the miR-124 could reverse the effects. Finally, NEAT1 regulated the H9c2 cells As2O3 injury by repressing the miR-124, NF-kappa B expressions and inflammatory response.
Conclusions: According to the results, we found that long non-coding RNA NEAT1 regulated the expression of inflammatory factors to protect cardiomyocytes from As2O3 damage by inhibiting miR-124/NF-kappa B signaling pathway. It provides a novel potential treatment strategy for As2O3 cardiomyocytes injury.