TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival

Lucia Micale, Carmela Fusco, Andrea Fontana, Raffaela Barbano, Bartolomeo Augello, Pasquelena De Nittis, Massimiliano Copetti, Maria Teresa Pellico, Barbara Mandriani, Dario Cocciadiferro, Paola Parrella, Vito Michele Fazio, Lucia Maria Cecilia Dimitri, Vincenzo D’Angelo, Chiara Novielli, Lidia Larizza, Antonio Daga, Giuseppe Merla

Human gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in glioma. TRIM8 transcriptional level was profiled in our own glioma cases collection by qPCR and confirmed in the independent TCGA glioma cohort. The association between TRIM8 expression and Overall Survival and Progression-free Survival in TCGA cohort was determined by using uni-multivariable Cox regression analysis. The effect of TRIM8 on patient glioma cell proliferation was evaluated by performing MTT and clonogenic assays. The mechanisms causing the reduction of TRIM8 expression were explored by using qPCR and in vitro assays. We showed that TRIM8 expression correlates with unfavorable clinical outcome in glioma patients. We found that a restored TRIM8 expression induced a significant reduction of clonogenic potential in U87MG and patient's glioblastoma cells. Finally we provide experimental evidences showing that miR-17 directly targets the 3' UTR of TRIM8 and post-transcriptionally represses the expression of TRIM8. Our study provides evidences that TRIM8 may participate in the carcinogenesis and progression of glioma and that the transcriptional repression of TRIM8 might have potential value for predicting poor prognosis in glioma patients.