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

Abstract

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.

• Authors: Ying Huang, Yang Yang, Yong He, Cheng Huang, Xiaoming Meng, Jun Li
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 22 Issue 31 Pg. 4868-4875 ( 2016) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 26861724 (Publication Type: Journal Article)

Chemical References

• MIRN208 microRNA, rat
• MicroRNAs
• RNA, Messenger
• Angiotensin II
• NLK protein, rat
• Protein Serine-Threonine Kinases

Topics

• Angiotensin II (metabolism)
• Animals
• Apoptosis (genetics)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Male
• MicroRNAs (genetics)
• Myoblasts, Cardiac (cytology, enzymology, metabolism)
• Protein Serine-Threonine Kinases (biosynthesis, genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Structure-Activity Relationship