Journal
ONCOTARGET
Volume 6, Issue 20, Pages 18105-18115Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3906
Keywords
ATRX; DNA methylation; chromosome end; MGMT; biological behaviors
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Funding
- National High Technology Research and Development Program (863) [2012AA02A508]
- Research Special Fund For Public Welfare Industry of Heath [201402008]
- International Science and Technology Cooperation Program [2012DFA30470]
- National Natural Science Foundation of China [91229121, 81201993]
- Beijing Science and Technology Plan [Z131100006113018]
- National Key Technology Research and Development Program of the Ministry of Science and Technology of China [2013BAI09B03]
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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-igh 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.
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