WT1-AS promotes cell apoptosis in hepatocellular carcinoma through down-regulating of WT1

Background: the antisense of the tumor suppressor gene wt1 (wt1-as) is a long non-coding rna. the role of wt1-as in the development of hepatocellular carcinoma (hcc) has not yet been elucidated. methods: quantitative real-time pcr and western blot analyses were used to measure levels of wt1-as and its related genes in tumor and corresponding adjacent tumor tissues of hcc patients. the effect on hcc cell proliferation and apoptosis was assessed by edu incorporation assays and pi-annexin-v staining,respectively. shrna and dual-luciferase assays were used to investigate the regulatory relationship between wt1-as and wt1 in cell lines. results: wt1-as expression correlated negatively with wt1 expression in hcc tumor tissue. kaplan-meier curve analysis revealed that wt1-as expression is a reliable indicator of hcc prognosis. the downregulation of wt1 expression by wt1-as promoted cell apoptosis by suppressing the jak/stat3 signaling pathway. bioinformatics analysis showed that wt1-as downregulates wt1 by binding to the tata region of the wt1 promotor. wt1-as was also able to reverse wt1-mediated resistance to dox based chemotherapy in hcc cells. conclusions: wt1-as downregulates wt1 expression in hcc tumors and promotes apoptosis by binding to the promoter region of wt1. our findings suggest that wt1-as may function as a tumor suppressor in hcc by reversing the oncogenic effects of wt1. © 2015 lv et al.