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.
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.
School of Pharmacy, Experimental Medicine Section, University of Camerino, Camerino (MC), Italy.
Massimo
M
Nabissi
Department of Molecular Medicine, Sapienza University, Rome (RM), Italy.
Maria Beatrice
MB
Morelli
I.N.M. Neuromed, Pozzilli, Isernia (IS), Italy.
Antonietta
A
Arcella
Department of Molecular Medicine, Sapienza University, Rome (RM), Italy.
Claudio
C
Cardinali
Department of Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona (AN), Italy.
Matteo
M
Santoni
Department of Molecular Medicine, Sapienza University, Rome (RM), Italy.|I.N.M. Neuromed, Pozzilli, Isernia (IS), Italy.
Giovanni
G
Bernardini
Department of Molecular Medicine, Sapienza University, Rome (RM), Italy.|I.N.M. Neuromed, Pozzilli, Isernia (IS), Italy.
Angela
A
Santoni
School of Pharmacy, Experimental Medicine Section, University of Camerino, Camerino (MC), Italy.
Giorgio
G
Santoni
School of Biosciences and Veterinary Medicine, University of Camerino, Camerino (MC), Italy.
Consuelo
C
Amantini
D020121:5' Untranslated Regions; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006207:Half-Life; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053208:Kaplan-Meier Estimate; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009690:Nucleic Acid Conformation; D016016:Proportional Hazards Models; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D007371:Interferon-gamma; D020123:Sirolimus
5’UTR; TRPV1; glioblastoma; prognosis; survival rate