PMID- 23386720
OWN - NLM
STAT- MEDLINE
DCOM- 20130426
LR  - 20220409
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 110
IP  - 8
DP  - 2013 Feb 19
TI  - Critical regulation of miR-200/ZEB2 pathway in Oct4/Sox2-induced 
      mesenchymal-to-epithelial transition and induced pluripotent stem cell 
      generation.
PG  - 2858-63
LID - 10.1073/pnas.1212769110 [doi]
AB  - Fibroblasts can be reprogrammed to induced pluripotent stem cells (iPSCs) by 
      application of transcription factors octamer-binding protein 4 (Oct4), SRY-box 
      containing gene 2 (Sox2), Kruppel-like factor 4 (Klf4), and c-Myelocytomatosis 
      oncogene (c-Myc) (OSKM), but the underlying mechanisms remain unclear. Here, we 
      report that exogenous Oct4 and Sox2 can bind at the promoter regions of 
      mir-141/200c and mir-200a/b/429 cluster, respectively, and induce the 
      transcription activation of miR-200 family during the OSKM-induced reprogramming. 
      Functional suppression of miR-200s with specific inhibitors significantly 
      represses the OSKM-caused mesenchymal-to-epithelial transition (MET, an early 
      event in reprogramming of fibroblasts to iPSCs) and iPSC generation, whereas 
      overexpression of miR-200s promotes the MET and iPSC generation. Mechanistic 
      studies showed that miR-200s significantly repress the expression of zinc finger 
      E-box binding homeobox 2 (ZEB2) through directly targeting its 3' UTR and direct 
      inhibition of ZEB2 can mimic the effects of miR-200s on iPSC generation and MET 
      process. Moreover, the effects of miR-200s during iPSC generation can be blocked 
      by ZEB2 overexpression. Collectively, our findings not only reveal that members 
      of the miR-200 family are unique mediators of the reprogramming factors 
      Oct4/Sox2, but also demonstrate that the miR-200/ZEB2 pathway as one critical 
      mechanism of Oct4/Sox2 to induce somatic cell reprogramming at the early stage.
FAU - Wang, Guiying
AU  - Wang G
AD  - Clinical and Translational Research Center of Shanghai First Maternity and Infant 
      Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, 
      School of Life Science and Technology, Tongji University, Shanghai 200092, 
      People's Republic of China.
FAU - Guo, Xudong
AU  - Guo X
FAU - Hong, Wujun
AU  - Hong W
FAU - Liu, Qidong
AU  - Liu Q
FAU - Wei, Tingyi
AU  - Wei T
FAU - Lu, Chenqi
AU  - Lu C
FAU - Gao, Longfei
AU  - Gao L
FAU - Ye, Dan
AU  - Ye D
FAU - Zhou, Yi
AU  - Zhou Y
FAU - Chen, Jie
AU  - Chen J
FAU - Wang, Jianmin
AU  - Wang J
FAU - Wu, Minjuan
AU  - Wu M
FAU - Liu, Houqi
AU  - Liu H
FAU - Kang, Jiuhong
AU  - Kang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130205
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Klf4 protein, mouse)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn200 microRNA, mouse)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (Pou5f1 protein, mouse)
RN  - 0 (Repressor Proteins)
RN  - 0 (SOXB1 Transcription Factors)
RN  - 0 (Sox2 protein, mouse)
RN  - 0 (ZEB2 protein, mouse)
RN  - 0 (Zinc Finger E-box Binding Homeobox 2)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - *Epithelial-Mesenchymal Transition
MH  - Homeodomain Proteins/*metabolism
MH  - Kruppel-Like Factor 4
MH  - Mice
MH  - MicroRNAs/*metabolism
MH  - Octamer Transcription Factor-3/*metabolism
MH  - Pluripotent Stem Cells/*cytology/metabolism
MH  - Promoter Regions, Genetic
MH  - Repressor Proteins/*metabolism
MH  - SOXB1 Transcription Factors/*metabolism
MH  - Zinc Finger E-box Binding Homeobox 2
PMC - PMC3581874
COIS- The authors declare no conflict of interest.
EDAT- 2013/02/07 06:00
MHDA- 2013/04/27 06:00
PMCR- 2013/08/19
CRDT- 2013/02/07 06:00
PHST- 2013/02/07 06:00 [entrez]
PHST- 2013/02/07 06:00 [pubmed]
PHST- 2013/04/27 06:00 [medline]
PHST- 2013/08/19 00:00 [pmc-release]
AID - 1212769110 [pii]
AID - 201212769 [pii]
AID - 10.1073/pnas.1212769110 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2858-63. doi: 
      10.1073/pnas.1212769110. Epub 2013 Feb 5.