Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico de...

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Autores principales: Josane F Sousa, Raul Torrieri, Rodrigo R Silva, Cristiano G Pereira, Valeria Valente, Erico Torrieri, Kamila C Peronni, Waleska Martins, Nair Muto, Guilherme Francisco, Carla Abdo Brohem, Carlos G Carlotti, Silvya S Maria-Engler, Roger Chammas, Enilza M Espreafico
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Publicado: Public Library of Science (PLoS) 2010
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spelling oai:doaj.org-article:61b2293f2ad346c1a792d5a0e19781322021-11-18T07:03:06ZNovel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.1932-620310.1371/journal.pone.0013510https://doaj.org/article/61b2293f2ad346c1a792d5a0e19781322010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20975957/?tool=EBIhttps://doaj.org/toc/1932-6203Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.Josane F SousaRaul TorrieriRodrigo R SilvaCristiano G PereiraValeria ValenteErico TorrieriKamila C PeronniWaleska MartinsNair MutoGuilherme FranciscoCarla Abdo BrohemCarlos G CarlottiSilvya S Maria-EnglerRoger ChammasEnilza M EspreaficoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 10, p e13510 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Josane F Sousa
Raul Torrieri
Rodrigo R Silva
Cristiano G Pereira
Valeria Valente
Erico Torrieri
Kamila C Peronni
Waleska Martins
Nair Muto
Guilherme Francisco
Carla Abdo Brohem
Carlos G Carlotti
Silvya S Maria-Engler
Roger Chammas
Enilza M Espreafico
Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.
description Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.
format article
author Josane F Sousa
Raul Torrieri
Rodrigo R Silva
Cristiano G Pereira
Valeria Valente
Erico Torrieri
Kamila C Peronni
Waleska Martins
Nair Muto
Guilherme Francisco
Carla Abdo Brohem
Carlos G Carlotti
Silvya S Maria-Engler
Roger Chammas
Enilza M Espreafico
author_facet Josane F Sousa
Raul Torrieri
Rodrigo R Silva
Cristiano G Pereira
Valeria Valente
Erico Torrieri
Kamila C Peronni
Waleska Martins
Nair Muto
Guilherme Francisco
Carla Abdo Brohem
Carlos G Carlotti
Silvya S Maria-Engler
Roger Chammas
Enilza M Espreafico
author_sort Josane F Sousa
title Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.
title_short Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.
title_full Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.
title_fullStr Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.
title_full_unstemmed Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.
title_sort novel primate-specific genes, rmel 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/61b2293f2ad346c1a792d5a0e1978132
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