RGD Reference Report - MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation. - Rat Genome Database

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MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation.

Authors: Luo, X  Pan, Z  Shan, H  Xiao, J  Sun, X  Wang, N  Lin, H  Xiao, L  Maguy, A  Qi, XY  Li, Y  Gao, X  Dong, D  Zhang, Y  Bai, Y  Ai, J  Sun, L  Lu, H  Luo, XY  Wang, Z  Lu, Y  Yang, B  Nattel, S 
Citation: Luo X, etal., J Clin Invest. 2013 May 1;123(5):1939-51. doi: 10.1172/JCI62185. Epub 2013 Apr 1.
RGD ID: 7247428
Pubmed: PMID:23543060   (View Abstract at PubMed)
PMCID: PMC3635715   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI62185   (Journal Full-text)

Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced morbidity and mortality. Inward-rectifier K+ current (IK1) is believed to be an important regulator of reentrant-spiral dynamics and a major component of AF-related electrical remodeling. MicroRNA-26 (miR-26) is predicted to target the gene encoding KIR2.1, KCNJ2. We found that miR-26 was downregulated in atrial samples from AF animals and patients and this downregulation was accompanied by upregulation of IK1/KIR2.1 protein. miR-26 overexpression suppressed expression of KCNJ2/KIR2.1. In contrast, miR-26 knockdown, inhibition, or binding-site mutation enhanced KCNJ2/KIR2.1 expression, establishing KCNJ2 as a miR-26 target. Knockdown of endogenous miR-26 promoted AF in mice, whereas adenovirus-mediated expression of miR-26 reduced AF vulnerability. Kcnj2-specific miR-masks eliminated miR-26-mediated reductions in Kcnj2, abolishing miR-26's protective effects, while coinjection of a Kcnj2-specific miR-mimic prevented miR-26 knockdown-associated AF in mice. Nuclear factor of activated T cells (NFAT), a known actor in AF-associated remodeling, was found to negatively regulate miR-26 transcription. Our results demonstrate that miR-26 controls the expression of KCNJ2 and suggest that this downregulation may promote AF.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
atrial fibrillation  IEP 7247428mRNA:increased expression:heart atriumRGD 
atrial fibrillation  ISOKCNJ2 (Homo sapiens)7247428; 7247428mRNA:increased expression:heart atriumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Kcnj2  (potassium inwardly-rectifying channel, subfamily J, member 2)

Genes (Mus musculus)
Kcnj2  (potassium inwardly-rectifying channel, subfamily J, member 2)

Genes (Homo sapiens)
KCNJ2  (potassium inwardly rectifying channel subfamily J member 2)


Additional Information