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microRNA in cardiac arrhythmias
Author(s) -
Wang Jun,
Bai Yan,
Li Na,
Ye Wenduo,
Zhang Min,
Greene Stephanie B,
Tao Ye,
Chen Yiping,
Wehrens Xander H. T.,
Martin James F
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.372.3
Subject(s) - microrna , sinoatrial node , atrial fibrillation , gene silencing , homeobox , medicine , biology , gene expression , bioinformatics , gene , genetics , heart rate , blood pressure
microRNAs (miRs) are small endogenous non‐coding RNAs that function in biologic processes primarily via post‐transcriptional gene silencing. Previous genome‐wide association studies and mouse studies indicated homeobox gene Pitx2 as a predisposition gene of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. To identify miRs function in AF, we performed miR expression profiling and ChIP‐sequencing (ChIP‐Seq) using different Pitx2 alleles. We found that Pitx2 positively regulates miR‐17‐92 and its homologous cluster miR‐106b‐25 . Both miR‐17‐92 and miR‐106b‐25 deficient mice had pacing‐induced AF under programmed stimulation. Electrocardiogram telemetry further revealed that mice with miR‐17‐92 cardiac‐specific conditional knockout (CKO) developed prolonged PR intervals whereas mice with miR‐17‐92 cardiac‐specific CKO and miR‐106b‐25 heterozygosity developed sinoatrial node dysfunction(SND). Both arrhythmias are AF risk factors in humans. Importantly, miR‐17‐92 and miR‐106b‐25 directly repress the sinoatrial node (SAN)‐specific gene expression such as Shox2 and Tbx3 . Together, these findings provided a novel insight for miR function in prevention of AF. In addition, our most recent data indicated that miR‐17‐92 is active in the cardiac conduction system (CCS) and mice with miR‐17‐92 CCS‐specific CKO had cardiac arrhythmias, indicating a miR function in the CCS homeostasis. Support or Funding Information This work was supported by a 2012–2013 Michael Bilitch Fellowship in Cardiac Pacing and Electrophysiology from the Heart Rhythm Society (to J.W.), American Heart Association (AHA) Grant 14SDG19840000 (to J.W.), AHA Grant 12PRE11720003 (to Y.B.), AHA Grant 12BGIA12050207 (to N.L.), AHA Grant 13PRE13750003 (to W.Y.), National Institutes of Health (NIH) Grant 1F32HL105041 (to Y.T.), AHA Grant 13EIA14560061, NIH Grants R01‐HL089598 and R01‐HL091947, the Fondation Leducq Alliance for CaMKII Signaling in Heart (X.H.T.W.), NIH Grant 5R01HL118761 (to J.F.M.), NIH Grant R01DE17792 (to Y.C.), and the Vivian L. Smith foundation (J.F.M.).