title: The human RNA surveillance factor UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma.
abstract: BACKGROUND
  In spite of progress in diagnostics and treatment of Hepatocellular Carcinoma (HCC), its prognosis remains poor, and improved treatment strategies for HCC require detailed understanding of the underlying mechanism. In this investigation we studied the role of Up-frameshift 1 (UPF1) in the tumorigenesis of HCC.
  
  
  METHODS
  We determined the expression level of UPF1 in HCC tissues with quantitative real-time PCR and western blotting and then studied its clinical significance. Sodium bisulfite sequencing was used to investigate the regulation of UPF1. We explored the biological significance of UPF1 with gain-and-loss-of-function analyses both in vitro and in vivo. The relationship between UPF1 and SMAD7 was also investigated by western blotting and immunofluorescence.
  
  
  RESULTS
  A great downregulation of UPF1 due to promoter hypermethylation was observed in tumor tissues compared to their adjacent normal tissues. Meanwhile, patients with low UPF1 expression have significantly poorer prognosis than those with high expression. Functionally, UPF1 regulated HCC tumorigenesis both in vitro and in vivo. Moreover, the decreased UPF1 level in HCC reduces NMD efficiency and leads to up-regulation of Smad7, then affects the TGF-β pathway.
  
  
  CONCLUSIONS
  Our findings revealed that UPF1 is a potential tumor suppressive gene and may be a potential therapeutic target for HCC.
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. reniorchang@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.affiliation: Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation Donghu Road 169, Wuhan, 430071, China. 1006672622@qq.com.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. 345259934@qq.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. wdevali@whu.edu.cn.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. 469386903@qq.com.
authors.forename: Weijie
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. yuanyf1971@163.com.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. 407019815@qq.com.
authors.forename: Quanyan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation Donghu Road 169, Wuhan, 430071, China. whuyeqifa@163.com.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. liuzs53@163.com.
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D011379:Prognosis; D011401:Promoter Regions, Genetic; D020365:RNA Helicases; D051906:Smad7 Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
chemical_list: C497806:SMAD7 protein, human; D051906:Smad7 Protein; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human