TY - JOUR
T1 - TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival
AU - Micale, Lucia
AU - Fusco, Carmela
AU - Fontana, Andrea
AU - Barbano, Raffaela
AU - Augello, Bartolomeo
AU - De Nittis, Pasquelena
AU - Copetti, Massimiliano
AU - Pellico, Maria Teresa
AU - Mandriani, Barbara
AU - Cocciadiferro, Dario
AU - Parrella, Paola
AU - Fazio, Vito Michele
AU - Dimitri, Lucia Maria Cecilia
AU - D'Angelo, Vincenzo
AU - Novielli, Chiara
AU - Larizza, Lidia
AU - Daga, Antonio
AU - Merla, Giuseppe
PY - 2015/6/16
Y1 - 2015/6/16
N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Cell proliferation
KW - Glioblastoma
KW - miR-17
KW - TRIM8
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U2 - 10.1186/s12885-015-1449-9
DO - 10.1186/s12885-015-1449-9
M3 - Article
AN - SCOPUS:84931262859
SN - 1471-2407
VL - 15
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 470
ER -