title: MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta1 in neonatal rat ventricular myocytes.
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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Hitoo
authors.initials: H
authors.lastname: Nishi
authors.forename: Koh
authors.initials: K
authors.lastname: Ono
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horie
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagao
authors.forename: Minako
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: Shin
authors.initials: S
authors.lastname: Watanabe
authors.forename: Tomohide
authors.initials: T
authors.lastname: Takaya
authors.forename: Yodo
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Rieko
authors.initials: R
authors.lastname: Takanabe-Mori
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wada
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Kawamura
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C000594638:MYH7 protein, rat; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; C551613:Myh7 protein, mouse; D034741:RNA, Small Interfering; D037042:Thyroid Hormone Receptors beta; D043244:Ribonuclease III; D018995:Myosin Heavy Chains