title: Pygo2 functions as a prognostic factor for glioma due to its up-regulation of H3K4me3 and promotion of MLL1/MLL2 complex recruitment.
abstract: Pygo2 has been discovered as an important Wnt signaling component contributing to the activation of Wnt-target gene transcription. In the present study, we discovered that Pygo2 mRNA and protein levels were up-regulated in the majority of (152/209) human brain glioma tissues and five glioma cell lines, and significantly correlated with the age, the WHO tumor classification and poor patient survival. The histone methyltransferase complex components (WDR5, Ash2, and menin, but not CXCC1 or NCOA6) were down-regulated at the promoter loci of Wnt target genes after Pygo2 knockdown, and this was accompanied by the down-regulation of Wnt/β-catenin pathway activity. Further, we demonstrated that the involvement of Pygo2 in the activation of the Wnt pathway in human glioma progression is through up-regulation of the H3K4me3 (but not H3K4me2) by promoting the recruitment of the histone methyltransferase MLL1/MLL2 complex to Wnt target gene promoters. Thus, our study provided evidence that Pygo2 functions as a novel prognostic marker and represents a potential therapeutic target.
authors.affiliation: Membrane Protein Disease and Cancer Research Center, Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, Hubei, 430068, China.
authors.forename: Cefan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Membrane Protein Disease and Cancer Research Center, Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, Hubei, 430068, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Membrane Protein Disease and Cancer Research Center, Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, Hubei, 430068, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dai
authors.affiliation: Membrane Protein Disease and Cancer Research Center, Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, Hubei, 430068, China.
authors.forename: Mengzhou
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Neurology department, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, China.
authors.forename: Yefu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Membrane Protein Disease and Cancer Research Center, Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, Hubei, 430068, China.|Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
authors.forename: Xing-Zhen
authors.initials: XZ
authors.lastname: Chen
authors.affiliation: Membrane Protein Disease and Cancer Research Center, Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, Hubei, 430068, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Tang
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C485622:ASH2L protein, human; C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C497422:KMT2A protein, human; C120898:KMT2D protein, human; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C453401:PYGO2 protein, human; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C502547:WDR5 protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase