Post-transcriptional regulation of 5'-untranslated regions of human Transient Receptor Potential Vanilloid type-1 (TRPV-1) channels: role in the survival of glioma patients
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Massimo Nabissi1, Maria Beatrice Morelli2, Antonietta Arcella3, Claudio Cardinali2, Matteo Santoni4, Giovanni Bernardini2,3, Angela Santoni2,3, Giorgio Santoni1, Consuelo Amantini5
1School of Pharmacy, Experimental Medicine Section, University of Camerino, Camerino (MC), Italy
2Department of Molecular Medicine, Sapienza University, Rome (RM), Italy
3I.N.M. Neuromed, Pozzilli, Isernia (IS), Italy
4Department of Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona (AN), Italy
5School of Biosciences and Veterinary Medicine, University of Camerino, Camerino (MC), Italy
Massimo Nabissi, email: [email protected]
Consuelo Amantini, email: [email protected]
Keywords: TRPV1, glioblastoma, 5’UTR, survival rate, prognosis
Received: August 02, 2016 Accepted: October 14, 2016 Published: November 05, 2016
The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel is a non-selective 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.
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