Regulation of the SK3 channel by microRNA-499 - Potential role in atrial fibrillation

Tian You Ling, Xiao Li Wang, Qiang Chai, Tin Wah Lau, Celeste M. Koestler, Soon J. Park, Richard C. Daly, Kevin L. Greason, Jin Jen, Li Qun Wu, Wei Feng Shen, Win Kuang Shen, Yong Mei Cha, Hon Chi Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Background MicroRNAs are important regulators of gene expression, including those involving electrical remodeling in atrial fibrillation (AF). Recently, KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), was found to be strongly associated with AF. Objectives To evaluate the changes in atrial myocardial microRNAs in patients with permanent AF and to determine the role of microRNA on the regulation of cardiac SK3 expression. Methods Atrial tissue obtained during cardiac surgery from patients (4 sinus rhythm and 4 permanent AF) was analyzed by using microRNA arrays. Potential targets of microRNAs were predicted by using software programs. The effects of specific microRNAs on target gene expression were evaluated in HL-1 cells from a continuously proliferating mouse hyperplastic atrial cardiomyocyte cell line. Interactions between microRNAs and targets were further evaluated by using luciferase reporter assay and by using Argonaute pull-down assay. Results Twenty-one microRNAs showed significant (>2-fold) changes in AF. MicroRNA 499 (miR-499) was upregulated by 2.33-fold (P

Original languageEnglish (US)
Pages (from-to)1001-1009
Number of pages9
JournalHeart Rhythm
Volume10
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • Atrial fibrillation
  • Electrical remodeling
  • MicroRNA
  • SK3 channel
  • Small-conductance calcium-activated potassium channel

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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