title: Depletion of histone demethylase KDM5B inhibits cell proliferation of hepatocellular carcinoma by regulation of cell cycle checkpoint proteins p15 and p27.
abstract: BACKGROUND
  KDM5B is a jmjc domain-containing histone demethylase which remove tri-, di-, and monomethyl groups from histone H3 lysine 4 (H3K4). KDM5B has been determined as an oncogene in many malignancies. However, its expression and role in hepatocellular carcinoma (HCC) remain unknown.
  
  
  METHODS
  We detected the expression of KDM5B in HCC tissues and cell lines. Cell proliferation was performed to reveal the role of KDM5B depletion on HCC cells both in vivo and in vitro. Flow cytometry was used to analyze the cell cycle and chip analysis was conducted to determine the direct target of KDM5B.
  
  
  RESULTS
  KDM5B is frequently up-regulated in HCC specimens compared with adjacent normal tissues and its expression level was significantly correlated with tumor size, TNM stage, and Edmondson grade. Moreover, Kaplan-Meier survival analysis showed that patients with high levels of KDM5B expression had a relatively poor prognosis. Knockdown of KDM5B notably inhibits HCC cell proliferation both in vivo and in vitro via arresting the cell cycle at G1/S phase partly through up-regulation of p15 and p27. Further molecular mechanism study indicates that silencing of KDM5B promotes p15 and p27 expression by increasing histone H3K4 trimethylation in their promoters.
  
  
  CONCLUSIONS
  KDM5B could be a potentially therapeutic target, which provides a rationale for the development of histone demethylase inhibitors as a strategy against HCC.
authors.affiliation: Liver Transplantation Center, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Liver Transplantation Center, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
authors.affiliation: Liver Transplantation Center, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Jiao
authors.affiliation: Liver Transplantation Center, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Liver Transplantation Center, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Xinxiang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Liver Transplantation Center, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Yang
authors.affiliation: Liver Transplantation Center, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China. drxcli@njmu.edu.cn.
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics* / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D012097:Repressor Proteins / Q000378:metabolism*; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: C436291:CDKN1B protein, human; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D009687:Nuclear Proteins; D012097:Repressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human