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TRIM11 is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth

Oncogene volume 32, pages 5038–5047 (2013)Cite this article

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Abstract

TRIM11 (tripartite motif-containing protein 11), an E3 ubiquitin ligase, is known to be involved in the development of the central nervous system. However, very little is known regarding the role of TRIM11 in cancer biology. Here, we examined the expression profile of TRIM11, along with two stem cell markers CD133 and nestin, in multiple glioma patient specimens, glioma primary cultures derived from tumors taken at surgery and normal neural stem/progenitor cells (NSCs). The oncogenic function of TRIM11 in glioma biology was investigated by knockdown and/or overexpression in vitro and in vivo experiments. Our results showed that TRIM11 expression levels were upregulated in malignant glioma specimens and in high-grade glioma-derived primary cultures, whereas remaining low in glioblastoma multiforme (GBM) stable cell lines, low-grade glioma-derived primary cultures and NSCs. The expression pattern of TRIM11 strongly correlated with that of CD133 and nestin and differentiation status of malignant glioma cells. Knock down of TRIM11 inhibited proliferation, migration and invasion of GBM cells, significantly decreased epidermal growth factor receptor (EGFR) levels and mitogen-activated protein kinase activity, and downregulated HB-EGF (heparin-binding EGF-like growth factor) mRNA levels. Meanwhile, TRIM11 overexpression promoted a stem-like phenotype in vitro (tumorsphere formation) and enhanced glial tumor growth in immunocompromised mice. These findings suggest that TRIM11 might be an indicator of glioma malignancy and has an oncogenic function mediated through the EGFR signaling pathway. TRIM11 overexpression potentially leads to a more aggressive glioma phenotype, along with increased malignant tumor growth and poor survival. Taken together, clarification of the biological function of TRIM11 and pathways it affects may provide novel therapeutic strategies for treating malignant glioma patients.

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Acknowledgements

We thank Xing Gong for the preparation of glioma primary cultures, Dr Ronald C Kim for the neuropathological diagnosis of tumor samples and Dr Abhishek Chaturbedi for the organization of the tumor list used in the study. This work was supported by research funds donated by Ralph and Suzanne Stern and the Community Foundation of Jewish Federation. This study was also supported, in part, by start-up funds to DAB from the University of California, Irvine and the UCI Cancer Center Award Number P30CA062203 from the National Cancer Institute.

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Authors and Affiliations

  1. Department of Neurological Surgery, UC Irvine School of Medicine, Orange, CA, USA

    K Di, M E Linskey & D A Bota

  2. UC Irvine Chao Family Comprehensive Cancer Center, Orange, CA, USA

    M E Linskey & D A Bota

  3. Department of Neurology, UC Irvine School of Medicine, Orange, CA, USA

    D A Bota

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Correspondence to D A Bota.

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Di, K., Linskey, M. & Bota, D. TRIM11 is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. Oncogene 32, 5038–5047 (2013). https://doi.org/10.1038/onc.2012.531

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