Downloads: 267

Files in This Item:
File Description SizeFormat 
MCB.00581-10.pdf620.77 kBAdobe PDFView/Open
Title: MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta1 in neonatal rat ventricular myocytes.
Authors: Nishi, Hitoo
Ono, Koh  kyouindb  KAKEN_id
Horie, Takahiro  kyouindb  KAKEN_id
Nagao, Kazuya
Kinoshita, Minako
Kuwabara, Yasuhide  kyouindb  KAKEN_id
Watanabe, Shin  kyouindb  KAKEN_id
Takaya, Tomohide
Tamaki, Yodo
Takanabe-Mori, Rieko
Wada, Hiromichi
Hasegawa, Koji
Iwanaga, Yoshitaka
Kawamura, Teruhisa
Kita, Toru
Kimura, Takeshi  kyouindb  KAKEN_id
Author's alias: 尾野, 亘
Keywords: microRNA
cardiac myocytes
myosin heavy chain
thyroid hormone receptor
Issue Date: Feb-2011
Publisher: American Society for Microbiology
Journal title: Molecular and cellular biology
Volume: 31
Issue: 4
Start page: 744
End page: 755
Abstract: MicroRNAs (miRNAs), small noncoding RNAs, are negative regulators of gene expression and play important roles in gene regulation in the heart. To examine the role of miRNAs in the expression of the two isoforms of the cardiac myosin heavy chain (MHC) gene, α- and β-MHC, which regulate cardiac contractility, endogenous miRNAs were downregulated in neonatal rat ventricular myocytes (NRVMs) using lentivirus-mediated small interfering RNA (siRNA) against Dicer, an essential enzyme for miRNA biosynthesis, and MHC expression levels were examined. As a result, Dicer siRNA could downregulate endogenous miRNAs simultaneously and the β-MHC gene but not α-MHC, which implied that specific miRNAs could upregulate the β-MHC gene. Among 19 selected miRNAs, miR-27a was found to most strongly upregulate the β-MHC gene but not α-MHC. Moreover, β-MHC protein was downregulated by silencing of endogenous miR-27a. Through a bioinformatics screening using TargetScan, we identified thyroid hormone receptor β1 (TRβ1), which negatively regulates β-MHC transcription, as a target of miR-27a. Moreover, miR-27a was demonstrated to modulate β-MHC gene regulation via thyroid hormone signaling and to be upregulated during the differentiation of mouse embryonic stem (ES) cells or in hypertrophic hearts in association with β-MHC gene upregulation. These findings suggested that miR-27a regulates β-MHC gene expression by targeting TRβ1 in cardiomyocytes.
Rights: © 2011, American Society for Microbiology
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1128/MCB.00581-10
PubMed ID: 21149577
Appears in Collections:Journal Articles

Show full item record

Export to RefWorks

Export Format: 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.