Long Non-coding RNA HOXA11 Antisense Promotes Cell Proliferation and Invasion and Predicts Patient Prognosis in Serous Ovarian Cancer

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Abstract
The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novel HOXA11 antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC). HOXA11as expression 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 low HOXA11as expression group (n=102). To investigate the role of HOXA11as in cell proliferation, invasion, and migration, HOXA11as expression in ovarian cancer cells was knocked down using RNA interference. HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue (p < 0.05). Higher HOXA11as expression was significantly correlated with histological grade (p=0.017) and preoperative cancer antigen 125 (p=0.048). HOXA11as overexpression in SOC cells led to increased cell proliferation, invasion, and migration. Moreover, HOXA11as was 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 that HOXA11as was 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 high HOXA11as expression. These findings highlight the clinical significance of HOXA11as to 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.
Funding Information
  • National Research Foundation of Korea (2015R1A2A2A01008162, 2015R1C1-A2A01053516)
  • Ministry of Education, Science and Technology

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