Up-regulation of USP2a and FASN in gliomas correlates strongly with glioma grade.

Abstract

Gliomas are the most common neoplasms in the central nervous system. The lack of efficacy of glioma therapies necessitates in-depth studies of glioma pathology, especially of the underlying molecular mechanisms that transform normal glial cells into tumor cells. Here we report that a deubiquitinating enzyme, ubiquitin-specific protease 2a (USP2a), and its substrate, fatty acid synthase (FASN), are over-expressed in glioma tissue. Using real-time quantitative polymerase chain reaction (PCR), Western blot and immunohistochemistry, we examined the expression and cellular distribution of USP2a and FASN in human glioma tissues. The expression patterns of USP2a and FASN correlated with the pathologic and clinical characteristics of the patients. Real-time PCR analysis showed that the expression levels of USP2a and its substrate FASN were higher in high-grade (World Health Organization [WHO] grades III and IV) glioma tissues than in low-grade (WHO grades I and II) glioma tissues. Western blot analysis indicated that the average optical densitometry ratio of USP2a and its substrate FASN in high-grade gliomas was higher than in low-grade gliomas. Moreover, statistical analysis of grade-classified glioma samples showed that the level of USP2a and FASN expression increased with the elevation of the WHO grade of glioma. USP2a protein expression was detected in the nucleus of glioma tissues and an increase in expression was significantly associated with the elevation of the WHO grade of glioma by immunohistochemistry. These findings expand our understanding of the molecular profiling of glioma and could shed light on new diagnostic criteria for gliomas.

• Authors: Bang-Bao Tao, Hua He, Xiu-hua Shi, Chun-lin Wang, Wei-qing Li, Bing Li, Yan Dong, Guo-Han Hu, Li-Jun Hou, Chun Luo, Ju-xiang Chen, Huai-rui Chen, Yu-hong Yu, Qing-fang Sun, Yi-Cheng Lu
• Journal: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia (J Clin Neurosci) Vol. 20 Issue 5 Pg. 717-20 (May 2013) ISSN: 1532-2653 [Electronic] Scotland
• PMID: 23416128 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012. Published by Elsevier Ltd.

Chemical References

• Fatty Acid Synthases
• Endopeptidases
• USP2 protein, human
• Ubiquitin Thiolesterase

Topics

• Adult
• Astrocytoma (classification, enzymology, pathology)
• Brain Neoplasms (enzymology, pathology)
• Endopeptidases (biosynthesis)
• Fatty Acid Synthases (biosynthesis)
• Female
• Humans
• Male
• Middle Aged
• Severity of Illness Index
• Ubiquitin Thiolesterase
• Up-Regulation (physiology)