Abstract
// Xian-Zhao Zhang 1 , Gui-Ling Sun 1 , Xi-Dong Li 1 , Jing-Fang Li 1 and Qing-Rong Ji 1 1 Department of Cardiology, Linyi People’s Hospital, Linyi, P.R. China Correspondence to: Qing-Rong Ji, email: qingrong_jqr@163.com Keywords : long noncoding RNA; long intergenic non-protein coding RNA 936; NF-kappa-B inhibitor alpha; nuclear factor-kappa-B signaling pathway; myocardial infarction Received: June 07, 2017 Accepted: October 28, 2017 Epub: December 30, 2017 Abstract Objective: The study aimed to explore the protective effect of LINC00936 against myocardial infarction (MI) by targeting NFKBIA through the NF-κB signaling pathway. Methods: Gene Expression Omnibus and Multi Experiment Matrix website were employed for Bioinformatics prediction. MI mouse models were established. Ultrasonic cardiogram assessments were conducted to quantify cardiac function. TTC and TUNEL staining were conducted to observe infarct size and apoptosis of myocardial tissues. Myocardial cells were assigned into blank, NC, LINC00936 vector, NFKBIA vector, siRNA-LINC00936, siRNA-NFKBIA, LINC00936 vector + NFKBIA vector and siRNA-LINC00936 + siRNA-NFKBIA groups. RT-qPCR and Western blotting were performed to measure expression of LINC00936, NFKBIA, NF-κBp50, NF-κBp65 and IKKβ. MTT assay, flow cytometry and ELLSA were conducted to measure cell viability, cell cycle, apoptosis and inflammatory cytokine expression. Results: LINC00936 showed high expression in MI. NFKBIA was confirmed as the target gene of LINC00936 by dual-luciferase reporter gene assay and RNA-IP assay. Compared with the sham group, the MI group exhibited larger infarct sizes, increased apoptotic myocardial cells, over-expressions of LINC00936, NF-κBp50, NF-κBp65 and IKKβ as well as reductions in expressions of NFKBIA. LINC00936 inhibited the activation of the NF-κB signaling pathway by suppressing NFKBIA expression. Overexpression of NFKBIA reversed the up-regulation of the NF-κB signaling pathway-related gene expression, inhibition of myocardial cell growth, apoptosis of myocardial cells and increased expressions of inflammatory cytokines due to high LINC00936 expression. Conclusion: Our study provided evidence suggesting that LINC00936-targeted overexpression of NFKBIA exhibits protective ability against MI through the blockade of the NF-κB pathway in mice.
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