title: MicroRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB.
abstract: Previous studies on erythropoiesis revealed that microRNAs (miRNAs) play a critical role in erythroid differentiation. Given the abundance of identified miRNAs and the limited understanding of erythroid miRNAs, additional examination is required. Here, two sets of erythroid differentiation miRNome data were analysed to screen for novel erythroid-inhibiting miRNAs. MIR200A was selected based on its pattern of downregulated expression in the miRNome datasets during induction of erythroid differentiation. Overexpression of MIR200A in K562 and TF-1 cells confirmed its inhibitory role in erythroid differentiation. Further in vivo study indicated that overexpression of mir200a inhibited primitive erythropoiesis of zebrafish. Transcriptome analyses after MIR200A overexpression in TF-1 cells indicated a significant role in regulating erythroid function and revealed potential regulation networks. Additionally, bioinformatics and experimental analyses confirmed that PDCD4 (programmed cell death 4) and THRB (thyroid hormone receptor, beta) are both targets of MIR200A-3p. Gain- and loss-of-function studies of PDCD4 and THRB revealed that the two targets were capable of promoting erythroid gene expression. Overall, our results revealed that microRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB.
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Du
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Centre for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: ZhiChao
authors.initials: Z
authors.lastname: Lu
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Shuge
authors.initials: S
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ding
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Centre for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Binghao
authors.initials: B
authors.lastname: Bao
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|China National Committee for Terms in Sciences and Technologies, Beijing, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Qu
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Centre for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Jia
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D041905:Erythroid Cells / Q000166:cytology*; D004920:Erythropoiesis / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D035683:MicroRNAs / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors*; D037042:Thyroid Hormone Receptors beta / Q000037:antagonists & inhibitors*; D015027:Zebrafish
chemical_list: D051017:Apoptosis Regulatory Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D037042:Thyroid Hormone Receptors beta
keywords: RNA sequencing; erythroid differentiation; microRNA 200a; programmed cell death 4; thyroid hormone receptor, beta