Introduction: TRIM11 (tripartite motif-containing protein 11), a member of the TRIM/RBCC family of E3 ubiquitin ligases, is known to modulate neurogenesis and Alzheimer’s disease-related neurotoxicity through ubiquitin-mediated protein degradation pathways. Here we investigated the gene expression levels of TRIM11 in multiple glioma specimens and demonstrated an important role forTRIM11 in tumorigenesis of glioma cells.
Methods: Gene expression levels of TRIM11 and CD133, a stem cell marker, were determined by real-time RT-PCR in four glioblastoma cell lines, thirteen primary tumor cultures from glioma patients (Grade II to IV), and normal human neural stem/progenitor cell (NSPCs) cultures from three different patients. In addition, the oncogenic function of TRIM11 was studied in human glioblastoma cell lines by knocking down TRIM11 through RNA interference.
Results: While CD133 was up-regulated in NSPCs and in high grade glioma stem-like cells, TRIM11 was up-regulated only in high grade glioma stem-like cells, and its expression levels were low in glioblastoma stable cell lines, low grade glioma stem-like cells and NSPCs. Interestingly, high TRIM11 expression correlated with high CD133 expression in 4 out of 5 GBM samples, indicating that TRIM11 may be an new biomarker for cancer stem cells. Knock-down of TRIM11 inhibited proliferation, migration and invasion of glioma cells. Knock-down of TRIM11 also led to decreased EGFR levels and reduced MAPK activity.
Conclusions: Our study has identified TRIM11 as a new cancer stem cell marker in gliomas. TRIM is up-regulated in high grade glioma stem-like cells and likely exerts its oncogenic function on glioma cell proliferation, migration and invasion, through EGFR and the MAPK signaling pathway.
Patient Care: Identification of TRIM11 as a new cancer stem cell marker in gliomas will enhance our understanding of molecular mechanism of glioma oncogenesis and hopefully inch toward finding a better cure for patients suffering from glioma.
Learning Objectives: Tripartite Motif-Containing Protein 11 (TRIM11) has been identified as cancer stem cell markers in glioma patients. We aim to educate the scientific community about this noble biomarker for cancer stem cells and how it involved in oncogenesis of glioma.