%0 Journal Article %T SNPs at miR-155 binding sites of TYRP1 explain discrepancy between mRNA and protein and refine TYRP1 prognostic value in melanoma %+ Institut de Génétique et Développement de Rennes (IGDR) %+ Service d'anatomie pathologique [Bruxelles] %+ Institut de Génétique et Développement de Rennes (IGDR) %A El Hajj, P. %A Gilot, D. %A Migault, M. %A Theunis, A. %A Kempen, L. C., Van %A Salés, F. %A Fayyad-Kazan, H. %A Badran, B. %A Larsimont, D. %A Awada, A. %A Bachelot, L. %A Galibert, M.-D. %A Ghanem, G. %A Journe, F %< avec comité de lecture %@ 0007-0920 %J British Journal of Cancer %I Cancer Research UK %V 113 %N 1 %P 91--98 %8 2015 %D 2015 %R 10.1038/bjc.2015.194 %M 26068396 %Z Life Sciences [q-bio]Journal articles %X BACKGROUND: We previously demonstrated an inverse correlation between tyrosinase-related protein 1 (TYRP1) mRNA expression in melanoma metastases and patient survival. However, TYRP1 protein was not detected in half of tissues expressing mRNA and did not correlate with survival. Based on a study reporting that 3' untranslated region (UTR) of TYRP1 mRNA contains two miR-155-5p (named miR-155) binding sites exhibiting single-nucleotide polymorphisms (SNPs) that promote (matched miRNA-mRNA interaction) mRNA decay or not (mismatched), we aimed to investigate the role of miR-155 in the regulation of TYRP1 mRNA expression and protein translation accounting for these SNPs. METHODS: The effect of miR-155 on TYRP1 mRNA/protein expression was evaluated in two melanoma cell lines harbouring matched or mismatched miR-155-TYRP1 mRNA interaction after transfection with pre-miR-155. In parallel, 192 skin and lymph node melanoma metastases were examined for TYRP1 mRNA/protein, miR-155 and SNPs and correlated with patient survival. TYRP1 mRNA, SNPs at its 3'UTR and miR-155 were analysed by RT-qPCR, whereas TYRP1 protein was evaluated by western blot in cell lines and by immunohistochemistry in metastatic tissues. RESULTS: The miR-155 induced a dose-dependent TYRP1 mRNA decay and hampered its translation into protein in the line with the 'match' genotype. In melanoma metastases, TYRP1 mRNA inversely correlated with miR-155 expression but not with TYRP1 protein in the 'match' group, whereas it positively correlated with protein but not with miR-155 in the 'mismatch' group. Consequently, in the latter group, TYRP1 protein inversely correlated with survival. CONCLUSION: Polymorphisms in 3'UTR of TYRP1 mRNA can affect TYRP1 mRNA regulation by miR-155 and its subsequent translation into protein. These SNPs can render TYRP1 mRNA and protein expression nonsusceptible to miR-155 activity and disclose a prognostic value for TYRP1 protein in a subgroup of melanoma patients. These data support the interest in the prognostic value of melanogenic markers and propose TYRP1 to refine prognosis in patients with advanced disease %G English %2 https://univ-rennes.hal.science/hal-01175527/document %2 https://univ-rennes.hal.science/hal-01175527/file/bjc2015194.pdf %L hal-01175527 %U https://univ-rennes.hal.science/hal-01175527 %~ UNIV-RENNES1 %~ CNRS %~ IFR140 %~ IGDR %~ STATS-UR1 %~ IGDR-EGO %~ UR1-UFR-SVE %~ UR1-HAL %~ UR1-SDV %~ TEST-UNIV-RENNES %~ TEST-UR-CSS %~ UNIV-RENNES %~ UR1-BIO-SA