title: Long Non-coding RNAHOXA11Antisense Promotes Cell Proliferation and Invasion and Predicts Patient Prognosis in Serous Ovarian Cancer.
abstract: OBJECTIVE
  The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novelHOXA11antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC).
  
  
  METHODS
  HOXA11asexpression was examined in 129 SOC tissue samples by real time reverse transcription polymerase chain reaction. Clinicopathological factors and patient survival were compared between the high (n=27) and lowHOXA11asexpression group (n=102). To investigate the role ofHOXA11asin cell proliferation, invasion, and migration,HOXA11asexpression in ovarian cancer cells was knocked down using RNA interference.
  
  
  RESULTS
  HOXA11asexpression in cancer tissue was 77-fold higher than that of noncancerous tissue (p < 0.05). HigherHOXA11asexpression was significantly correlated with histological grade (p=0.017) and preoperative cancer antigen 125 (p=0.048).HOXA11asoverexpression in SOC cells led to increased cell proliferation, invasion, and migration. Moreover,HOXA11aswas associated with the expression of genes involved in cell invasion, migration, and epithelial-mesenchymal transition (EMT), including vascular endothelial growth factor, matrix metalloproteinase 9 (MMP-9), B-catenin, E-cadherin, Snail, Twist, and vimentin. Multivariate analysis revealed thatHOXA11aswas a prognostic factor of progressive disease and mortality (hazard ratio [HR], 1.730; p=0.043 and HR, 2.170; p=0.033, respectively). Progression-free and overall survival were significantly shorter in patients with highHOXA11asexpression.
  
  
  CONCLUSIONS
  These findings highlight the clinical significance ofHOXA11asto predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness via regulation of vascular endothelial growth factor (VEGF), MMP-9, and EMT-related mechanisms.
authors.affiliation: Department of Obstetrics and Gynecology, National Medical Center, Seoul, Korea.|Department of Obstetrics and Gynecology, Yonsei University Graduate School, Seoul, Korea.
authors.forename: Ga Won
authors.initials: GW
authors.lastname: Yim
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Lee Kyung
authors.initials: LK
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Wun
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Nam
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D012372:ROC Curve
chemical_list: C484298:HOXA11 protein, human; D018398:Homeodomain Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering
keywords: Cell proliferation; Long noncoding RNA; Ovarian neoplasms; Prognosis