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Published on: December 9, 2016
Identification and expression of a novel MDM4 splice variant in human glioma
Xiaowen Wang1, Ping Sheng, Xingzhong Guo
1Department of Neurosurgery, Shanghai Institute of Neurosurgery, PLA Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
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.
Insights
Researchers identified a novel MDM4-B mRNA variant in human gliomas. Its expression correlates with tumor stage, p53 mutation, and Ki-67 status, suggesting a role in glioma progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MDM4 (MDMX) protein interacts with tumor suppressor p53 and is structurally similar to MDM2.
- MDM4 gene overexpression and various isoforms are observed in human tumors.
- Aberrant mRNA transcripts of MDM4 in glioma warrant investigation for their clinical significance.
Purpose of the Study:
- To investigate the presence of aberrant MDM4 mRNA transcripts in human glioma.
- To analyze the association between MDM4 splicing variants and clinicopathological characteristics of glioma patients.
Main Methods:
- RT-PCR was employed to detect MDM4 mRNA splicing variants in 42 glioma tissues.
- Real-time PCR quantified the expression level of the novel MDM4-B variant.
- Statistical analysis correlated MDM4-B expression with tumor stage, p53 mutation, and Ki-67 status.
Main Results:
- Four distinct MDM4 transcript sizes were detected: full length-MDM4 (851 bp), MDM4-S (783 bp), MDM4-A (701 bp), and a novel MDM4-B (540 bp).
- MDM4-B was present in various glioma stages, but its presence did not correlate with malignancy.
- MDM4-B mRNA expression levels significantly correlated with tumor stages, p53 mutation, and Ki-67 status.
Conclusions:
- A novel MDM4 alternative splicing form, MDM4-B, was identified in human gliomas.
- MDM4-B expression is associated with key clinical and molecular markers of glioma.
- The novel MDM4-B variant may contribute to glioma tumorigenesis and progression.
