title: The role of RhoC in ovarian epithelial carcinoma: a marker for carcinogenesis, progression, prognosis, and target therapy.
abstract: BACKGROUND
  Ras homolog gene family member C (RhoC) is a small G protein/guanosine triphosphatase involved in tumor mobility, invasion, and metastasis.
  
  
  METHODS
  After RhoC siRNA transfection, we measured the changes in phenotypes and some relevant molecules in ovarian carcinoma cell, OVCAR3. The mRNA and protein expression of RhoC was detected in ovarian tumors.
  
  
  RESULTS
  RhoC siRNA transfection resulted in low growth, G1 arrest, and apoptotic induction in the OVCAR3 in comparison with the control and mock. Following RhoC knockdown, there was reduced mRNA or protein expression of protein kinase B (Akt), signal transducer and activator of transcription 3 (stat3), bcl-xL, surviving and phosphorylated p70S6 kinase (p-p70s6k), while the converse was true for Bax and caspase-3. Lovastatin induced apoptosis, suppressed proliferation, migration and invasion, and disrupted lamellipodia formation in OVCAR3. Lovastatin exposure induced lower RhoC, bcl-2, matrix metalloproteinase-9 (MMP-9), survivin, Akt, bcl-xL, vascular endothelial growth factor (VEGF), and p-p70s6k expression in OVCAR3 compared to the control, but higher caspase-3 and Bax expression. RhoC mRNA and protein expression was significantly higher in ovarian carcinoma than in benign tumors and normal ovary tissue (p<0.05) and was positively associated with dedifferentiation, FIGO staging and p-p70s6k expression of ovarian carcinoma (p<0.05).
  
  
  CONCLUSIONS
  The up-regulated RhoC expression may affect ovarian carcinogenesis and should be considered a good biomarker for the differentiation and progression of ovarian carcinoma. RhoC plays an important role in apoptosis by modulating the relevant genes and the phosphorylation of downstream p70s6k.
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China. yida.zhaoyang@163.com
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Gou
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Xiao
authors.forename: Zhe-Feng
authors.initials: ZF
authors.lastname: Niu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000077022:Survivin; D046888:Tissue Array Analysis; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D008148:Lovastatin; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein
keywords: Aggressive phenotypes; Ovarian carcinoma; P70S6 kinase; Pathobiological behavior; Prognosis; RhoC