Regulation of the SK3 channel by microRNA-499--potential role in atrial fibrillation.
Regulation of the SK3 channel by microRNA-499--potential role in atrial fibrillation.
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DOI：
10.1016/j.hrthm.2013.03.005
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发表时间：
2013-07
期刊：
影响因子：
5.5
通讯作者：
Lee, Hon-Chi
中科院分区：
文献类型：
--
作者：
Ling, Tian-You;Wang, Xiao-Li;Chai, Qiang;Lau, Tin-Wah;Koestler, Celeste M.;Park, Soon J.;Daly, Richard C.;Greason, Kevin L.;Jen, Jin;Wu, Li-Qun;Shen, Wei-Feng;Shen, Win-Kuang;Cha, Yong-Mei;Lee, Hon-Chi
关键词：
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. This study sought 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. Atrial tissue obtained during cardiac surgery from patients (4 sinus rhythm and 4 permanent AF) was analyzed by microRNA arrays. Potential targets of microRNAs were predicted by 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 luciferase reporter assay and by Argonaute pull-down assay. Twenty one microRNAs showed significant, greater than two-fold changes in AF. miR-499 was upregulated by 2.33 fold (P<0.01) in AF atria, whereas SK3 protein expression was down-regulated by 46% (P<0.05). Transfection of miR-499 mimic in HL-1 cells resulted in the downregulation of SK3 protein expression, while that of miR-499 inhibitor upregulated SK3 expression. Binding of miR-499 to the 3′UTR of KCNN3 was confirmed by luciferase reporter assay and by the enhanced presence of SK3 mRNA in Argonaute pulled-down microRNA-induced silencing complexes (mRISC) after transfection with miR-499. Atrial miRNA-499 is significantly upregulated in AF, leading to SK3 downregulation and possibly contributing to the electrical remodeling in AF.
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影响因子：
30.8
作者：
Ellinor, Patrick T.;Lunetta, Kathryn L.;Glazer, Nicole L.;Pfeufer, Arne;Alonso, Alvaro;Chung, Mina K.;Sinner, Moritz F.;de Bakker, Paul I. W.;Mueller, Martina;Lubitz, Steven A.;Fox, Ervin;Darbar, Dawood;Smith, Nicholas L.;Smith, Jonathan D.;Schnabel, Renate B.;Soliman, Elsayed Z.;Rice, Kenneth M.;Van Wagoner, David R.;Beckmann, Britt-M;van Noord, Charlotte;Wang, Ke;Ehret, Georg B.;Rotter, Jerome I.;Hazen, Stanley L.;Steinbeck, Gerhard;Smith, Albert V.;Launer, Lenore J.;Harris, Tamara B.;Makino, Seiko;Nelis, Mari;Milan, David J.;Perz, Siegfried;Esko, Tonu;Koettgen, Anna;Moebus, Susanne;Newton-Cheh, Christopher;Li, Man;Moehlenkamp, Stefan;Wang, Thomas J.;Kao, W. H. Linda;Vasan, Ramachandran S.;Noethen, Markus M.;MacRae, Calum A.;Stricker, Bruno H. Ch;Hofman, Albert;Uitterlinden, Andre G.;Levy, Daniel;Boerwinkle, Eric;Metspalu, Andres;Topol, Eric J.;Chakravarti, Aravinda;Gudnason, Vilmundur;Psaty, Bruce M.;Roden, Dan M.;Meitinger, Thomas;Wichmann, H-Erich;Witteman, Jacqueline C. M.;Barnard, John;Arking, Dan E.;Benjamin, Emelia J.;Heckbert, Susan R.;Kaeaeb, Stefan
通讯作者：
Kaeaeb, Stefan
影响因子：
20.1
作者：
Chua SK;Chang PC;Maruyama M;Turker I;Shinohara T;Shen MJ;Chen Z;Shen C;Rubart-von der Lohe M;Lopshire JC;Ogawa M;Weiss JN;Lin SF;Ai T;Chen PS
通讯作者：
Chen PS
影响因子：
4.8
作者：
Xu, YF;Tuteja, D;Chiamvimonvat, N
通讯作者：
Chiamvimonvat, N
影响因子：
5.5
作者：
Girmatsion, Zenawit;Biliczki, Peter;Ehrlich, Joachim R.
通讯作者：
Ehrlich, Joachim R.
DOI：
10.1111/j.1540-8167.2008.01357.x
发表时间：
2009-02-01
影响因子：
2.7
作者：
Latronico, Michael V. G.;Condorelli, Gianluigi
通讯作者：
Condorelli, Gianluigi