title: Identification and expression of a novel MDM4 splice variant in human glioma.
abstract: The product of the MDMX (or MDM4) gene is structurally related to the MDM2 oncoprotein and is also capable of interacting with the tumor suppressor protein p53. The MDM4 gene is overexpressed in several human tumors, while its product can be detected as various isoforms. This study was aimed to find the presence of aberrant mRNA transcripts of MDM4 in human glioma and their association with the clinicopathological characteristics of glioma patients. 42 glioma tissues were examined for MDM4 mRNA splicing variants by RT-PCR. A total of four distinct transcript sizes (full length-MDM4 851 bp, MDM4-S 783 bp, MDM4-A 701 bp, MDM4-B 540 bp) were detected. In the present study, we first report the novel alternative splicing form of MDM4, MDM4-B (GenBank accession no.KC479043.1). Expression of MDM4-B was present in various stages of human gliomas, but no significant correlation between presence of MDM4-B and malignancy of glioma was observed. The expression level of MDM4-B mRNA detected by real-time PCR was not only significantly associated with tumor stages, but also with p53 mutation and Ki-67 status which are important clinical molecular markers of glioma. Our data indicate that the novel variant MDM4-B may play a role in glioma tumorigenesis or cancer progression.
authors.affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, PLA Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Sheng
authors.forename: Xingzhong
authors.initials: X
authors.lastname: Guo
authors.forename: Junyu
authors.initials: J
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Hou
authors.forename: Guohan
authors.initials: G
authors.lastname: Hu
authors.forename: Chun
authors.initials: C
authors.lastname: Luo
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Lu
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D018797:Cell Cycle Proteins; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Alternative splicing; Glioma; MDM4; mRNA; p53