Identification and expression of a novel MDM4 splice variant in human glioma

• Published in: Brain research 2013-11, Vol.1537, p.260-266
• Main Authors: Wang, Xiaowen, Sheng, Ping, Guo, Xingzhong, Wang, Junyu, Hou, Lijun, Hu, Guohan, Luo, Chun, Dong, Yan, Lu, Yicheng
• Format: Article
• Language: English
• Subjects: Alternative splicing; Alternative Splicing - genetics; Biological and medical sciences; brain; carcinogenesis; Gene Expression Regulation, Neoplastic; gene overexpression; genes; genetic markers; Glioma; Glioma - genetics; Humans; MDM4; Medical sciences; mRNA; mutation; Mutation - genetics; neoplasms; Neurology; Nuclear Proteins - metabolism; oncogene proteins; p53; patients; Protein Isoforms - genetics; Proto-Oncogene Proteins - metabolism; quantitative polymerase chain reaction; RNA Splicing - genetics; RNA, Messenger - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors of the nervous system. Phacomatoses
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2013.07.054

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 851bp, MDM4-S 783bp, MDM4-A 701bp, MDM4-B 540bp) 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.