title: Placental growth factor promotes metastases of ovarian cancer through MiR-543-regulated MMP7.
abstract: OBJECTIVE
  Elucidation of the molecular mechanisms underlying ovarian cancer (OC) cell invasion and migration may provide important evidence for developing efficient therapy. Recently, Matrix metalloproteinase (MMP) has been shown to be regulated by vascular endothelial growth factor family members, especially placental growth factor (PLGF), as a potential mechanism underlying cancer invasion. Here, we studied the molecular relationship between PLGF and MMP7 in the OC.
  
  
  METHODS
  We examined the levels of PLGF and MMP7 in the resected OC specimens and compared to paired adjacent non-tumor ovarian tissue. We also examined the correlation between PLGF and MMP7. We modified PLGF levels in a human OC cell line, OVCAR3, and analyzed the effects on MMP7. Prediction of microRNA (miRNA) binding to 3'-UTR of MMP7 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay using miR-543-modifed OC cells. The levels of miR-543 were examined in the OC specimens, and the correlation between miR-543 and PLGF or MMP7 was performed.
  
  
  RESULTS
  PLGF and MMP7 both significantly increased in the OC specimens, compared to paired adjacent non-tumor ovarian tissue. PLGF significantly increased MMP7 in the OC cells at protein level, but not at mRNA level. In OC cells, PLGF significantly decreased the levels of miR-543, which suppressed the translation of MMP7 mRNA via 3'-UTR binding. In OC specimen, miR-543 significantly decreased, compared to paired adjacent non-tumor ovarian tissue. An inverse correlation was detected between the levels of miR-543 and PLGF or MMP7 in the OC specimens.
  
  
  CONCLUSIONS
  MiR-543 inhibits translation of MMP7 through binding to the 3'-UTR of MMP7 mRNA in OC. PLGF suppresses miR-543, which activates MMP7-mediated cancer invasion.
authors.forename: Ning
authors.initials: N
authors.lastname: Song
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Ma
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C577592:MIRN543 microRNA, human; D035683:MicroRNAs; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7