title: WT1-AS promotes cell apoptosis in hepatocellular carcinoma through down-regulating of WT1.
abstract: 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.
authors.affiliation: Department of General Surgery, People's Hospital of Gaochun, No. 9 Chunzhong Road, Gaochun, Nanjing, 211300, Jiangsu Province, China. l3851596501@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of General Surgery, People's Hospital of Gaochun, No. 9 Chunzhong Road, Gaochun, Nanjing, 211300, Jiangsu Province, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Yixing People's Hospital, the Affiliated Hospital of Jiangsu University, Yixing, 214200, Jiangsu Province, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Nanjing Jiangning Hospital, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 211100, Jiangsu Province, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of General Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, 210009, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D016373:DNA, Antisense / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016162:Genes, Wilms Tumor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D025721:WT1 Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D016373:DNA, Antisense; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human; D053612:Janus Kinases