Letter abstract


Nature Medicine 13, 486 - 491 (2007)
Published online: 1 April 2007 | Corrected online: 6 December 2011 | Corrected online: 6 December 2011 | doi:10.1038/nm1569



There is a Addendum (December 2011) associated with this Letter.
There is a Corrigendum (December 2011) associated with this Letter.

The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2

Baofeng Yang1,2,5, Huixian Lin2,3,4,5, Jiening Xiao2,3,4,5, Yanjie Lu1,2, Xiaobin Luo2,3,4, Baoxin Li1, Ying Zhang1, Chaoqian Xu1, Yunlong Bai1, Huizhen Wang1,3, Guohao Chen1 & Zhiguo Wang2,3,4

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MicroRNAs (miRNAs) are endogenous noncoding RNAs, about 22 nucleotides in length, that mediate post-transcriptional gene silencing by annealing to inexactly complementary sequences in the 3′-untranslated regions of target mRNAs1, 2, 3. Our current understanding of the functions of miRNAs relies mainly on their tissue-specific or developmental stage-dependent expression and their evolutionary conservation, and therefore is primarily limited to their involvement in developmental regulation and oncogenesis2. Of more than 300 miRNAs that have been identified, miR-1 and miR-133 are considered to be muscle specific4, 5, 6. Here we show that miR-1 is overexpressed in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis. Elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis. miR-1 overexpression slowed conduction and depolarized the cytoplasmic membrane by post-transcriptionally repressing KCNJ2 (which encodes the K+ channel subunit Kir2.1) and GJA1 (which encodes connexin 43), and this likely accounts at least in part for its arrhythmogenic potential. Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target.

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  1. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150086, China.
  2. Institute of Cardiovascular Research, Harbin Medical University, Harbin, Heilongjiang 150086, China.
  3. Research Center, Montreal Heart Institute, 5000 Belanger East, Montreal PQ H1T 1C8, Canada.
  4. Department of Medicine, University of Montreal, Montreal PQ H3C 3J7, Canada.
  5. These authors contributed equally to this work.

Correspondence to: Zhiguo Wang2,3,4 e-mail: wz.email@gmail.com

Correspondence to: Baofeng Yang1,2,5 e-mail: yangbf@ems.hrbmu.edu.cn

*
In the version of this article initially published, lanes from the original blot shown in Figure 2b (NIZ and IZ samples, blotting for 55-kDa Kir2.1 and GAPDH) were rearranged in the published figure. The two lanes at the far right of the published blot were on the far left of the original blot, so that the sequence of the lanes in the original blot was as follows (from left to right): IZ (WT miR-1 + AMO-1), IZ (MT miR-1), NIZ, IZ, IZ (AMO-1), IZ (WT miR-1). We have added white space to indicate that the blot is not continuous in the HTML and PDF versions of the article.


**
Editors' note: With regard to the above article, the editors wish to notify readers of Nature Medicine that the Montreal Heart Institute announced on 2 September 2011 that an investigation had found evidence of misconduct in publications from the laboratory of Zhiguo Wang at that institution. The committee in charge of this investigation recommended that several publications from Z. Wang's laboratory be retracted (some of which had already been retracted over the summer); in addition, his laboratory at the Montreal Heart Institute was closed. One of the papers investigated was the Nature Medicine paper listed above, for which the corresponding authors were Z. Wang (affiliated with the Harbin Medical University, China and the Montreal Heart Institute, Canada) and Baofeng Yang (affiliated with the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China and the Institute of Cardiovascular Research, Harbin Medical University, China). The investigating committee's report stated that they did not find evidence of misconduct for the data in the Nature Medicine paper that was generated at the Montreal Heart Institute; namely, Figure 1a ("CAD human" data only) and Figure 2f,g. According to the report, the remaining data in the paper were not generated at the Montreal Heart Institute and were not investigated. In correspondence with Nature Medicine, both Z. Wang and Yang stand by the data in the Nature Medicine paper. However, Z. Wang noted that, for Figure 2b, lanes from the original blot had been rearranged in the published figure, for which we are publishing a Corrigendum in this issue.

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