Genome biology · 2021
Ten-eleven translocation protein 1 modulates medulloblastoma progression.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kim Hyerim, Kang Yunhee, Li Yujing, Chen Li, Lin Li, Johnson Nicholas D, Zhu Dan, Robinson M Hope, McSwain Leon, Barwick Benjamin G, Yuan Xianrui, Liao Xinbin, Zhao Jie, Zhang Zhiping, Shu Qiang, Chen Jianjun, Allen Emily G, Kenney Anna M, Castellino Robert C, Van Meir Erwin G, Conneely Karen N, Vertino Paula M, Jin Peng, Li Jian
Аннотация
BACKGROUND: Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes.
RESULTS: We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes.
CONCLUSIONS: These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.
RESULTS: We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes.
CONCLUSIONS: These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.
Предметные рубрики MeSH
5-MethylcytosineAnimalsBiomarkers, TumorComputational BiologyCpG IslandsDNA MethylationDatabases, Nucleic AcidDisease Models, AnimalDisease ProgressionDisease SusceptibilityEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMedulloblastomaMiceMice, TransgenicMixed Function OxygenasesNucleotide MotifsPrognosisProto-Oncogene Proteins