title: JARID1B deletion induced apoptosis in Jeko-1 and HL-60 cell lines.
abstract: OBJECTIVE
  To investigate the involvement of JARID1B histone methyltransferase in the epigenetic change of euchromatic promoter in mantle cell lymphoma (MCL) and acute leukemia.
  
  
  METHODS
  We retrospectively analyzed the protein of JARID1B and tri-methylated histone H3 lysine 4 (H3K4), histone H3 lysine 9 (H3K9), and cyclin D1 and Ki67 in 30 cases of MCL by immunohistochemistry. JARID1B was depleted by small interfering RNA (siRNA), and cell apoptosis and cell proliferation were detected by flow cytometry and MTT [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide], histone tri-methylated H3K4 and histone acetylated H3, H4, cyclin D1, Bcl-2, procaspase-3, C-myc were studied by Western blot.
  
  
  RESULTS
  We demonstrated that JARID1B was upregulated and histone tri-methylated H3K4 was downregulated in MCL compared to proliferative lymphadenitis, P < 0.05. The expression of histone methylated H3K9 was similar in both. Histone methylation of H3K4 was positively correlated with Ki67 in MCL (Kappa = 0.757, P < 0.05). This study showed that depletion of JARID1B cleavage apoptotic proteins of Bcl-2, procaspase-3, C-myc and resulted in loss cell viability and inducing apoptosis in Jeko-1 and HL-60 cell lines. JARID1B siRNA improved tri-methyl H3K4 and histone acetylated H3 and inhibited cyclin D1, but did not affect histone acetylated H4.
  
  
  CONCLUSIONS
  This study revealed hyper JARID1B expression and hypo histone H3K4 tri-methylation in MCL. We identify depletion JARID1B as a demethylase which is capable of removing three methyl groups from H3K4 and up-regulating histone acetylation of H3 in both cell lines. Interestingly, depletion of JARID1B inhibits Cyclin D1, which is one of the genes contributes to MCL pathogenesis. JARID1B might be one of therapeutic targets in acute leukemia and MCL.
authors.affiliation: Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University Zhangzhou, Fujian, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Hematology Zhangzhou Affiliated Hospital of Fujian Medical University Zhangzhou, Fujian, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Hematology Zhangzhou Affiliated Hospital of Fujian Medical University Zhangzhou, Fujian, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Hematology Zhangzhou Affiliated Hospital of Fujian Medical University Zhangzhou, Fujian, China.
authors.forename: Huidan
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Hematology Zhangzhou Affiliated Hospital of Fujian Medical University Zhangzhou, Fujian, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zou
authors.affiliation: School of Basic Medical Sciences, Southern Medical University Guangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics; D005434:Flow Cytometry; D006657:Histones / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human
keywords: JARID1B; MCL; acute leukemia; histone methylation; siRNA