The impact of long non-coding RNA HOXA11 antisense on cell proliferation, invasion, and patient prognosis in epithelial ovarian cancer

Abstract

HOXA11 antisense (HOXA11as) RNA is a long non-coding RNA (lncRNA) which is transcribed from the antisense strand of the gene encoding homeobox gene HOXA 11. Since the functions of lncRNAs are only partially understood, we investigated the expression of HOXA11as and its functional role in serous ovarian cancer. HOXA11as expression was examined by real time RT-PCR and the results were compared with clinicopathologic factors including patient survival data. To determine the role of HOXA11as in cell proliferation, migration, and invasion, RNA interference was used to knockdown HOXA11as expression in ovarian cancer cells. HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue (P < 0.05). According to the relative HOXA11as expression in tumor tissues, 129 SOC patients were divided into high expression group (N = 27) and relatively low expression group (N = 102). Higher HOXA11as expression was significantly associated with histologic grade (P = 0.017) and preoperative tumor marker CA125 (P = 0.048). In multivariate analysis, progression-free survival and overall survival in ovarian cancer was significantly shorter in cases with high HOXA11as expression (HR = 1.730, 2.170 and P = 0.043, 0.033, respectively). HOXA11as overexpression in SOC cells led to increased cell proliferation, migration and invasion. In addition, the metastatic effects of HOXA11as was correlated to the expression of a number of genes involved in cell migration, invasion and epithelial-mesenchymal transition, including VEGF, MMP-9, E-cadherin, B-catenin, Vimentin, Snail and Twist. In conclusion, these findings highlight the clinical significance of HOXA11as in predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness through regulation of VEGF, MMP-9 and EMT-related mechanisms.