title: Mitotic arrest deficient protein MAD2B is overexpressed in human glioma, with depletion enhancing sensitivity to ionizing radiation.
abstract: Mitotic arrest deficient protein MAD2B, an enzyme involved in translesion DNA synthesis, has been implicated in several cancers. However, its role in human glioma has not been defined. In the present study, we investigated the expression levels of MAD2B in human gliomas and normal brain tissues, and determined whether depletion of MAD2B enhanced the sensitivity of glioma cells to ionizing radiation. Using reverse transcription-polymerase chain reaction and immunohistochemical analysis, MAD2B was found to be overexpressed in glioma specimens compared with normal brain tissue. Silencing of MAD2B markedly reduced clonogenic survival of glioma cells and significantly enhanced apoptosis in response to ionizing radiation. This effect was associated with caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, disruption of MAD2B potentiated radiation-induced genomic damage, as evidenced by increased phosphorylation of gamma histone H2AX (γ-H2AX). Our findings reveal that expression of MAD2B is deregulated in glioma, and targeting MAD2B may be a potential strategy for improving the efficacy of radiotherapy.
authors.affiliation: Department of Minimally Invasive Neurosurgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Shuizhong
authors.initials: S
authors.lastname: Liu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Tiejiang
authors.initials: T
authors.lastname: Kang
authors.forename: Zhanyi
authors.initials: Z
authors.lastname: Li
authors.forename: Hemin
authors.initials: H
authors.lastname: Deng
authors.forename: Wu
authors.initials: W
authors.lastname: Yue
authors.forename: Shujie
authors.initials: S
authors.lastname: Cao
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D004249:DNA Damage / Q000528:radiation effects; D053938:DNA Fragmentation / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D064246:Mad2 Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing
chemical_list: C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D011506:Proteins; D012333:RNA, Messenger