MicroRNA‑34a mediates atrial fibrillation through regulation of Ankyrin‑B expression.

Abstract

Atrial fibrillation (AF) has a high prevalence and recurrence rate, and is associated with substantial mortality. However, its underlying mechanisms are not thoroughly understood. Increasing attention has been paid to the roles of microRNAs (miRs) in the pathogenesis of cardiovascular disease, including miR‑1 and miR‑133 (in the electrophysiological response), and miR‑34a (in cardiac fibrosis). Recently, Ankyrin‑B (Ank‑B), an adaptor protein, has been demonstrated to be associated with AF. As a predicted target gene of miR‑34a, the present study aimed to investigate if miR‑34a has a role in AF via regulation of Ank‑B expression. Western blot analysis revealed that the expression levels of Ank‑B was lower in the atrial tissue of AF patients than in individuals with sinus rate (SR); however, reverse transcription‑quantitative polymerase chain reaction data demonstrated that miR‑34a expression exhibited the opposite pattern. Dual‑luciferase assays following the specific overexpression or inhibition of miR‑34a indicated that the 3' untranslated region of Ankyrin 2 (the gene encoding Ank‑B) contained binding sites for miR‑34a. Furthermore, the expression levels of Ank‑B and sodium‑calcium exchanger 1 (an Ank‑B binding partner important in Ca2+ homeostasis), as well as intracellular Ca2+ signaling detected by Fluoro‑3 AM, were altered following the modulation of miR‑34a expression. Thus, miR‑34a may serve an important role in early electrophysiological remodeling and the development of AF via the regulation of Ank‑B expression. These results offer valuable insight into the underlying mechanism of AF, and provide a promising target for developing clinical diagnostic tools and potential therapies for patients with AF.

• Authors: Yun Zhu, Zezhou Feng, Wei Cheng, Yingbin Xiao
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 17 Issue 6 Pg. 8457-8465 (Jun 2018) ISSN: 1791-3004 [Electronic] Greece
• PMID: 29658562 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• ANK2 protein, human
• Ankyrins
• Biomarkers
• MIRN34 microRNA, human
• MicroRNAs
• RNA, Messenger
• Sodium-Calcium Exchanger
• sodium-calcium exchanger 1
• Calcium

Topics

• 3' Untranslated Regions
• Aged
• Ankyrins (genetics)
• Atrial Fibrillation (diagnosis, genetics)
• Biomarkers
• Calcium (metabolism)
• Female
• Gene Expression Regulation
• Heart Function Tests
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• RNA Interference
• RNA, Messenger (genetics)
• Sodium-Calcium Exchanger (genetics, metabolism)