title: Loss of ATRX, associated with DNA methylation pattern of chromosome end, impacted biological behaviors of astrocytic tumors.
abstract: Loss of ATRX leads to epigenetic alterations, including abnormal levels of DNA methylation at repetitive elements such as telomeres in murine cells. We conducted an extensive DNA methylation and mRNA expression profile study on a cohort of 82 patients with astrocytic tumors to study whether ATRX expression was associated with DNA methylation level in astrocytic tumors and in which cellular functions it participated. We observed that astrocytic tumors with lower ATRX expression harbored higher DNA methylation level at chromatin end and astrocytic tumors with ATRX-low had distinct gene expression profile and DNA methylation profile compared with ATRX-high tumors. Then, we uncovered that several ATRX associated biological functions in the DNA methylation and mRNA expression profile (GEP), including apoptotic process, DNA-dependent positive regulation of transcription, chromatin modification, and observed that ATRX expression was companied by MGMT methylation and expression. We also found that loss of ATRX caused by siRNA induced apoptotic cells increasing, reduced tumor cell proliferation and repressed the cell migration in glioma cells. Our results showed ATRX-related regulatory functions of the combined profiles from DNA methylation and mRNA expression in astrocytic tumors, and delineated that loss of ATRX impacted biological behaviors of astrocytic tumor cells, providing important resources for future dissection of ATRX role in glioma.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cai
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Chinese Glioma Cooperative Group (CGCG), Beijing, China.|Department of Pathology, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000328:Adult; D017209:Apoptosis; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002877:Chromosomes, Human; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000075924:X-linked Nuclear Protein
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein; D045643:DNA Repair Enzymes
keywords: ATRX; DNA methylation; MGMT; biological behaviors; chromosome end