TY - JOUR
T1 - Post-transcriptional regulation of 5'-untranslated regions of human Transient Receptor Potential Vanilloid type-1 (TRPV-1) channels
T2 - Role in the survival of glioma patients
AU - Nabissi, Massimo
AU - Morelli, Maria Beatrice
AU - Arcella, Antonietta
AU - Cardinali, Claudio
AU - Santoni, Matteo
AU - Bernardini, Giovanni
AU - Santoni, Angela
AU - Santoni, Giorgio
AU - Amantini, Consuelo
PY - 2016
Y1 - 2016
N2 - The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel is a nonselective cation channel belonging to the Transient Receptor Potential family; variation of its expression has been correlated to glioma progression. In human, TRPV1 transcripts display a remarkable homogeneity differing only for the 5'-untranslated region (5'UTR) sequence that generates four variants encoding the same protein. Herein, we investigated the role of the 5'UTR sequences in TRPV1 transcripts stability, regulation of translation, expression in glioma cells and tissues. In addition, the expression of 5'UTR TRPV1 variants as prognostic factor in the survival of glioblastoma patients was evaluated. The expression level for each 5'UTR and their stability was evaluated by RT-PCR analysis. The effect of rapamycin and interferon-gamma in 5'UTR-regulating TRPV1 translation was determined by western blot analysis in glioma cell lines. We demonstrated that the 5'UTR influences the stability and translation efficacy of TRPV1 transcripts, and that TRPV1 variant three (TRPV1v3) was the most stable and the only variant expressed in GBM samples and in glioma stem-like cells. Furthermore, we found that TRPV1v3 expression levels correlate with patient's survival, suggesting that it may represent a potential prognostic marker for patients with glioma.
AB - The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel is a nonselective cation channel belonging to the Transient Receptor Potential family; variation of its expression has been correlated to glioma progression. In human, TRPV1 transcripts display a remarkable homogeneity differing only for the 5'-untranslated region (5'UTR) sequence that generates four variants encoding the same protein. Herein, we investigated the role of the 5'UTR sequences in TRPV1 transcripts stability, regulation of translation, expression in glioma cells and tissues. In addition, the expression of 5'UTR TRPV1 variants as prognostic factor in the survival of glioblastoma patients was evaluated. The expression level for each 5'UTR and their stability was evaluated by RT-PCR analysis. The effect of rapamycin and interferon-gamma in 5'UTR-regulating TRPV1 translation was determined by western blot analysis in glioma cell lines. We demonstrated that the 5'UTR influences the stability and translation efficacy of TRPV1 transcripts, and that TRPV1 variant three (TRPV1v3) was the most stable and the only variant expressed in GBM samples and in glioma stem-like cells. Furthermore, we found that TRPV1v3 expression levels correlate with patient's survival, suggesting that it may represent a potential prognostic marker for patients with glioma.
KW - 5'UTR
KW - Glioblastoma
KW - Prognosis
KW - Survival rate
KW - TRPV1
UR - http://www.scopus.com/inward/record.url?scp=85001129226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85001129226&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.13132
DO - 10.18632/oncotarget.13132
M3 - Article
AN - SCOPUS:85001129226
VL - 7
SP - 81541
EP - 81554
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 49
ER -