Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

Autor(es):Mostrar menos -

Sousa, Josane F. ^[1] ; Torrieri, Raul ^[1] ; Silva, Rodrigo R. ^[1] ; Pereira, Cristiano G. ^[1] ; Valente, Valeria ^[2] ; Torrieri, Erico ^[1] ; Peronni, Kamila C. ^[1] ; Martins, Waleska ^[3] ; Muto, Nair ^[3] ; Francisco, Guilherme ^{[4, 5]} ; Brohem, Carla Abdo ^[6] ; Carlotti, Jr., Carlos G. ^[2] ; Maria-Engler, Silvya S. ^[6] ; Chammas, Roger ^{[4, 5]} ; Espreafico, Enilza M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cirurgia & Anat, Sao Paulo - Brazil

^[3] AC Camargo Hosp Melanoma Grp, Div Pathol, Mol Biol Grp, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Dept Radiol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 5, n. 10 OCT 20 2010.
• Citações Web of Science: 11

Resumo

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. (AU)

• Processo FAPESP: 07/50604-9 - Caracterizacao global do perfil de expressao genica dos estagios inicial e avancado do melanoma e analise funcional de candidatos a supressor de tumor ou oncogene:consolidando ferramentas e dados...
• Beneficiário: Josane de Freitas Sousa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 06/60328-6 - Caracterização global do perfil de expressão gênica dos estágios inicial e avançado do melanoma e análise funcional de candidatos a supressor de tumor ou oncogênese: consolidando ferramentas e dados revelados em estudos prévios
• Beneficiário: Josane de Freitas Sousa
• Modalidade de apoio: Auxílio à Pesquisa - Programa Primeiros Projetos
• Processo FAPESP: 08/56521-0 - Identificacao de um novo gene pro-profilerativo associado com a progressao do melanoma e a mutacao ativadora de braf.
• Beneficiário: Cristiano Gonçalves Pereira
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 05/60026-7 - Caracterizacao funcional de novos genes com marcante expressao diferencial na progressao de melanoma detectada por microarranjo de cdna orestes.
• Beneficiário: Kamila Chagas Peronni
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 07/57307-0 - O gene KIAA0090 é ativado em lesão pré-neoplásica e seu silenciamento por siRNA causa morte celular em linhagem de melanoma
• Beneficiário: Rodrigo Ribeiro da Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado