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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

MicroRNA-208a Potentiates Angiotensin II-triggered Cardiac Myoblasts Apoptosis via Inhibiting Nemo-like Kinase (NLK)

Author(s): Ying Huang, Yang Yang, Yong He, Cheng Huang, Xiaoming Meng and Jun Li

Volume 22, Issue 31, 2016

Page: [4868 - 4875] Pages: 8

DOI: 10.2174/1381612822666160210143047

Price: $65


Introduction: MicroRNA-208a (miR-208a) exacerbated cardiomyocyte apoptosis via inhibiting nemo-like kinase (NLK). miR-208a is a crucial molecule in the regulation of heart diseases, however, the biological function and underlying mechanism of miR-208a in the progression of cardiomyocyte apoptosis is not clearly elucidated. We hypothesized that miR-208a might potentiate cardiomyocyte apoptosis through inhibiting NLK. Methods: Male Sprague-Dawley rats were underwent permanent coronary artery ligation to establish myocardial infarction (MI) model. The quantitative real-time RT-PCR (qRT-PCR) was used to evaluate the expression of miR-208a and NLK mRNA. Western blot was applied to detect NLK and Bcl-2 proteins expression. Luciferase reporter assay was performed to indentify NLK as a target of miR-208a. The apoptosis of H9C2 cells was assessed by flow cytometry (FCM). Results: miR-208a was upregulated accompanying with a significant decrease of NLK in response to MI, and stronger miR-208a staining was detected by in situ hybridization in the cytoplasm of cardiomyocytes in MI group compared to the sham group. In vitro, overexpression of miR-208a greatly enhance Ang II-induced the apoptosis of H9C2 cells through downregulating of NLK and the anti-apoptosis protein Bcl-2 expression, whereas these effects were reversed when miR-208a was downregulated. Dual luciferase reporter assay and western blot results demonstrated that NLK was a direct target of miR-208a. Interestingly, upregulation of NLK obviously increased Bcl-2 expression and reduced the percentage of apoptotic cells, while attenuation of NLK reduced the level of Bcl-2 and cells apoptosis after treatment with Ang II. Conclusions: miR-208a can promote Ang II-induced cardiomyocyte apoptosis via negatively regulating NLK expression, and inhibition of miR-208a may provide a novel therapeutic target for cardiomyocyte apoptosis.

Keywords: microRNA-208a, nemo-like kinase, apoptosis, angiotensin II, acute myocardial infarction.

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