Silencing of ATP2B1-AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA-mediated NF-κB signalling pathway.

Kai-You Song, Xian-Zhao Zhang, Feng Li, Qing-Rong Ji

Journal of cellular and molecular medicine 2020 Apr

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Myocardial infarction (MI) is an acute coronary syndrome that refers to tissue infarction of the myocardium. This study aimed to investigate the effect of long intergenic non-protein-coding RNA (lincRNA) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) against MI by targeting nuclear factor-kappa-B inhibitor alpha (NFKBIA) and mediating the nuclear factor-kappa-B (NF-κB) signalling pathway. An MI mouse model was established and idenepsied by cardiac function evaluation. It was determined that ATP2B1-AS1 was highly expressed, while NFKBIA was poorly expressed and NF-κB signalling pathway was activated in MI mice. Cardiomyocytes were extracted from mice and introduced with a series of mouse ATP2B1-AS1 vector, NFKBIA vector, siRNA-mouse ATP2B1-AS1 and siRNA-NFKBIA. The expression of NF-κBp50, NF-κBp65 and IKKβ was determined to idenepsy whether ATP2B1-AS1 and NFKBIA affect the NF-κB signalling pathway, the results of which suggested that ATP2B1-AS1 down-regulated the expression of NFKBIA and activated the NF-κB signalling pathway in MI mice. Based on the data from assessment of cell viability, cell cycle, apoptosis and levels of inflammatory cytokines, either silencing of mouse ATP2B1-AS1 or overexpression of NFKBIA was suggested to result in reduced cardiomyocyte apoptosis and expression of inflammatory cytokines, as well as enhanced cardiomyocyte viability. Our study provided evidence that mouse ATP2B1-AS1 silencing may have the potency to protect against MI in mice through inhibiting cardiomyocyte apoptosis and inflammation, highlighting a great promise as a novel therapeutic target for MI. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Citation

Kai-You Song, Xian-Zhao Zhang, Feng Li, Qing-Rong Ji. Silencing of ATP2B1-AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA-mediated NF-κB signalling pathway. Journal of cellular and molecular medicine. 2020 Apr;24(8):4466-4479