PMID- 25119590
OWN - NLM
STAT- MEDLINE
DCOM- 20150417
LR  - 20211021
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 35
IP  - 11
DP  - 2014 Nov
TI  - Molecular regulation of ovarian cancer cell invasion.
PG  - 11359-66
LID - 10.1007/s13277-014-2434-7 [doi]
AB  - The molecular mechanism underlying ovarian cancer invasiveness and metastasis 
      remains unclear. Since significant downregulation in microRNA 200 (miRNA200) 
      family (miR200a, miR200b, and miR200c) has been reported in the invasive ovarian 
      cancer cells, here, we used two human ovarian cancer cell lines, OVCAR3 and 
      SKOV3, to study the molecular basis of miR200, matrix metalloproteinase 3 (MMP3) 
      activation, and cancer invasiveness. We found that overexpression of either 
      miR200 family member in OVCAR3 or SKOV3 cells significantly inhibited production 
      and secretion of MMP3 and cancer invasiveness. Moreover, forced MMP3 expression 
      abolished miR200-induced inhibition of ovarian cancer cell invasiveness, 
      suggesting that miR200 family inhibited ovarian cell invasiveness via 
      downregulating MMP3. Furthermore, ZEB1, a major target of miR200, was inhibited 
      by miR200 overexpression. Forced ZEB1 expression abolished miR200-induced 
      inhibition of ovarian cancer cell invasiveness, suggesting that ZEB1 is a direct 
      target of miR200 for inhibiting ovarian cell invasiveness. Finally, 
      phosphorylated SMAD3 (pSMAD3), a major partner of ZEB1, was efficiently inhibited 
      by miR200, which could be restored by forced expression of ZEB1, but not by 
      forced expression of MMP3, suggesting that ZEB1/pSMAD3 is signaling cascade 
      upstream of MMP3 in this model. Taken together, our data suggest that miR200 
      family inhibited ovarian cancer cell invasiveness and metastasis by 
      downregulating MMP3, possibly through ZEB1/pSMAD3.
FAU - Sun, Ningxia
AU  - Sun N
AD  - Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, Second 
      Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
FAU - Zhang, Qing
AU  - Zhang Q
FAU - Xu, Chen
AU  - Xu C
FAU - Zhao, Qian
AU  - Zhao Q
FAU - Ma, Yan
AU  - Ma Y
FAU - Lu, Xinmei
AU  - Lu X
FAU - Wang, Liang
AU  - Wang L
FAU - Li, Wen
AU  - Li W
LA  - eng
PT  - Journal Article
DEP - 20140815
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MIRN200 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (Smad3 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (ZEB1 protein, human)
RN  - 0 (Zinc Finger E-box-Binding Homeobox 1)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Blotting, Western
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - MicroRNAs/*genetics
MH  - Neoplasm Invasiveness
MH  - Ovarian Neoplasms/genetics/metabolism/*pathology
MH  - Phosphorylation
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Smad3 Protein/genetics/*metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - Zinc Finger E-box-Binding Homeobox 1
EDAT- 2014/08/15 06:00
MHDA- 2015/04/18 06:00
CRDT- 2014/08/15 06:00
PHST- 2014/07/27 00:00 [received]
PHST- 2014/08/04 00:00 [accepted]
PHST- 2014/08/15 06:00 [entrez]
PHST- 2014/08/15 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
AID - 10.1007/s13277-014-2434-7 [doi]
PST - ppublish
SO  - Tumour Biol. 2014 Nov;35(11):11359-66. doi: 10.1007/s13277-014-2434-7. Epub 2014 
      Aug 15.