PMID- 27929537
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20181113
IS  - 2041-4889 (Electronic)
VI  - 7
IP  - 12
DP  - 2016 Dec 8
TI  - Upregulation of MiR-205 under hypoxia promotes epithelial-mesenchymal transition 
      by targeting ASPP2.
PG  - e2517
LID - 10.1038/cddis.2016.412 [doi]
AB  - The epithelial-mesenchymal transition (EMT) is one of the crucial procedures for 
      cancer invasion and distal metastasis. Despite undergoing intensive studies, the 
      mechanisms underlying EMT remain to be completely elucidated. Here, we identified 
      that apoptosis-stimulating protein of p53-2 (ASPP2) is a novel target of MiR-205 
      in various cancers. Interestingly, the binding site of MiR-205 at the 
      3'-untranslated region of ASPP2 was highly conserved among different species. An 
      inverse correlation between MiR-205 and ASPP2 was further observed in vivo in 
      cervical cancers, suggesting MiR-205 may be an important physiological inhibitor 
      of ASPP2. Hypoxia is a hallmark of solid tumor microenvironment and one of such 
      conditions to induce EMT. Notably, MiR-205 was remarkably induced by hypoxia in 
      cervical and lung cancer cells. A marked suppression of ASPP2 was observed 
      simultaneously. Further studies confirmed that hypoxia-induced ASPP2 suppression 
      was mainly attributed to the elevated MiR-205. Interestingly, the alteration of 
      MiR-205/ASPP2 under hypoxia was accompanied with the decreased epithelial marker 
      E-cadherin and increased mesenchymal marker Vimentin, as well as a morphological 
      transition from the typical cobblestone-like appearance to the mesenchymal-like 
      structure. More importantly, MiR-205 mimics or ASPP2 silencing similarly promoted 
      EMT process. By contrast, ASPP2 recovery or MiR-205 inhibitor reversed 
      MiR-205-dependent EMT. Further studies demonstrated that the newly revealed 
      MiR-205/ASPP2 axis promoted cell migration and also increased cell proliferation 
      both in vivo and in vitro. These data together implicated a critical impact of 
      MiR-205/ASPP2 on promoting EMT. MiR-205/ASPP2 may be potential diagnostic and 
      therapeutic biomarkers in cervical and lung cancers.
FAU - Wang, Xingwen
AU  - Wang X
AD  - School of Life Science and Technology, Harbin Institute of Technology, Shenzhen, 
      China.
AD  - Shenzhen Graduate School of Harbin Institute of Technology, Shenzhen, China.
FAU - Yu, Miao
AU  - Yu M
AD  - School of Chemical Engineering and Technology, Harbin Institute of Technology, 
      Harbin, China.
FAU - Zhao, Kunming
AU  - Zhao K
AD  - School of Life Science and Technology, Harbin Institute of Technology, Shenzhen, 
      China.
FAU - He, Mengmeng
AU  - He M
AD  - School of Life Science and Technology, Harbin Institute of Technology, Shenzhen, 
      China.
FAU - Ge, Wenjie
AU  - Ge W
AD  - School of Life Science and Technology, Harbin Institute of Technology, Shenzhen, 
      China.
AD  - Shenzhen Graduate School of Harbin Institute of Technology, Shenzhen, China.
FAU - Sun, Yuhui
AU  - Sun Y
AD  - The First Affiliated Hospital, Harbin Medical University, Harbin, China.
FAU - Wang, Yihua
AU  - Wang Y
AUID- ORCID: 0000-0001-5561-0648
AD  - Biological Sciences, Faculty of Natural and Environmental Sciences, University of 
      Southampton, Southampton, UK.
FAU - Sun, Haizhu
AU  - Sun H
AD  - The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
FAU - Hu, Ying
AU  - Hu Y
AD  - School of Life Science and Technology, Harbin Institute of Technology, Shenzhen, 
      China.
AD  - Shenzhen Graduate School of Harbin Institute of Technology, Shenzhen, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161208
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (MIRN205 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (TP53BP2 protein, human)
SB  - IM
MH  - Animals
MH  - Apoptosis Regulatory Proteins/*genetics/metabolism
MH  - Base Sequence
MH  - Cell Hypoxia/genetics
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - Epithelial-Mesenchymal Transition/*genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice, Nude
MH  - MicroRNAs/*genetics/metabolism
MH  - Models, Biological
MH  - Signal Transduction/genetics
MH  - Up-Regulation/*genetics
PMC - PMC5261019
EDAT- 2016/12/09 06:00
MHDA- 2017/09/19 06:00
PMCR- 2016/12/01
CRDT- 2016/12/09 06:00
PHST- 2016/07/29 00:00 [received]
PHST- 2016/10/24 00:00 [revised]
PHST- 2016/11/10 00:00 [accepted]
PHST- 2016/12/09 06:00 [entrez]
PHST- 2016/12/09 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - cddis2016412 [pii]
AID - 10.1038/cddis.2016.412 [doi]
PST - epublish
SO  - Cell Death Dis. 2016 Dec 8;7(12):e2517. doi: 10.1038/cddis.2016.412.