title: miR-200b targets GATA-4 during cell growth and differentiation.
abstract: GATA-4 is an important transcription factor involved in several developmental processes of the heart, such as cardiac myocyte proliferation, differentiation and survival. The precise mechanisms underlying the regulation of GATA-4 remain unclear, this is especially true for the mechanisms that mediate the post-transcriptional regulation of GATA-4. Here, we demonstrate that miR-200b, a member of the miR-200 family, is a critical regulator of GATA-4. Overexpression of miR-200b leads to the downregulation of GATA-4 mRNA and a decrease in GATA-4 protein levels. Moreover, miR-200b not only inhibits cell growth and differentiation but also reverses the growth response mediated by GATA-4, whereas depletion of miR-200b leads to a slight reversal of the anti-growth response achieved by knocking down endogenous GATA-4. More importantly, the cell cycle-associated gene cyclin D1, which is a downstream target of GATA-4, is also regulated by miR-200b. Thus, miR-200b targets GATA-4 to downregulate the expression of cyclin D1 and myosin heavy chain (MHC), thereby regulating cell growth and differentiation.
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou City, China.
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yao
authors.forename: Qing-Xia
authors.initials: QX
authors.lastname: Wei
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
authors.forename: Li-Xiang
authors.initials: LX
authors.lastname: Xue
authors.forename: Fen
authors.initials: F
authors.lastname: Yang
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhang
authors.forename: Cheng-Juan
authors.initials: CJ
authors.lastname: Xiong
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Li
authors.forename: Zhi-Ru
authors.initials: ZR
authors.lastname: Wei
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Ming-Xi
authors.initials: MX
authors.lastname: Zang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D019938:Cyclin D1; D018995:Myosin Heavy Chains
keywords: GATA-4; cell differentiation; cell growth; miR-200b; transcription regulation
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