title: Regulation of pigmentation by microRNAs: MITF-dependent microRNA-211 targets TGF-β receptor 2.
abstract: There is growing evidence that microRNAs are important regulators of gene expression in a variety of cell types. Using immortalized cell lines and primary neural crest cell explants, we show that microRNA-211, previously implicated in the regulation of melanoma proliferation and invasiveness, promotes pigmentation in melanoblasts and melanocytes. Expression of this microRNA is regulated by the key melanocyte transcription factor MITF and regulates pigmentation by targeting the TGF-β receptor 2. Transfection with pre-miR-211 precursor molecules in melb-a and melan-a cells leads to a decrease in the expression of TGF-β receptor 2 and reduces the TGF-β signaling-mediated downregulation of two melanogenic enzymes, tyrosinase and tyrosinase-related protein 1. Conversely, downregulation of microRNA-211 using specific microRNA inhibitors has the opposite effects. It appears, therefore, that microRNA-211 serves as a negative regulator of TGF-β signaling which is known to play a important roles in vivo in melanocyte stem cell maintenance and pigmentation.
authors.affiliation: Developmental Cell Biology and Disease Program, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, China; Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Dai
authors.forename: Chunbao
authors.initials: C
authors.lastname: Rao
authors.forename: Huirong
authors.initials: H
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Lilv
authors.initials: L
authors.lastname: Fan
authors.forename: Huiqin
authors.initials: H
authors.lastname: Geng
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Ling
authors.initials: L
authors.lastname: Hou
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D008969:Molecular Sequence Data; D010858:Pigmentation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D008543:Melanins; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor; C577982:Mirn211 microRNA, mouse; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: TGF-β signaling; hyperpigmentation; melanocyte; miRNA; pigmentation