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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Quantitative proteomic analysis and functional studies reveal that nucleophosmin is involved in cell death in glioblastoma cell line transfected with siRNA

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Autor(es):
Gimenez, Marcela [1, 2, 3] ; Marie, Suely K. N. [4] ; Oba-Shinjo, Sueli M. [4] ; Uno, Miyuki [4] ; da Silva, Roseli [4] ; Laure, Helen Julie [1, 2, 3] ; Izumi, Clarice [1, 2, 3] ; Otake, Andreia [5] ; Chammas, Roger [5] ; Rosa, Jose Cesar [1, 2, 3]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Prot Chem Ctr, BR-14049 Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Mol & Cell Biol & Pathogen Bioagents, BR-14049 Ribeirao Preto - Brazil
[3] Fundacao Hemoctr Ribeira Preto, CEPID CTC Ctr Cell Therapy, Ribeirao Preto - Brazil
[4] Univ Sao Paulo, Med Sch Sao Paulo, Dept Neurol, Sao Paulo - Brazil
[5] Univ Sao Paulo, Med Sch Sao Paulo, Dept Radiol & Oncol, Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: PROTEOMICS; v. 12, n. 17, SI, p. 2632-2640, AUG 2012.
Citações Web of Science: 5
Resumo

Previously, we reported that nucleophosmin (NPM) was increased in glioblastoma multiforme (GBM). NPM is a phosphoprotein related to apoptosis, ribosome biogenesis, mitosis, and DNA repair, but details about its function remain unclear. We treated U87MG and A172 cells with small interference RNA (siRNA) and obtained a reduction of 80% in NPM1 expression. Knockdown at the protein level was evident after the 4th day and was maintained until the 7th day of transfection that was investigated by quantitative proteomic analysis using isobaric tags. The comparison of proteomic analysis of NPM1-siRNA against controls allowed the identification of 14 proteins, two proteins showed increase and 12 presented a reduction of expression levels. Gene ontology assigned most of the hypoexpressed proteins to apoptosis regulation, including GRP78. NPM1 silencing did not impair cell proliferation until the 7th day after transfection, but sensitized U87MG cells to temozolomide (TMZ), culminating with an increase in cell death and provoking at a later period a reduction of colony formation. In a large data set of GBM patients, both GRP78 and NPM1 genes were upregulated and presented a tendency to shorter overall survival time. In conclusion, NPM proved to participate in the apoptotic process, sensitizing TMZ-treated U87MG and A172 cells to cell death, and in association with upregulation of GRP78 may be helpful as a predictive factor of poor prognosis in GBM patients. (AU)

Processo FAPESP: 08/51360-9 - Proteômica funcional: estudo do papel da nucleofosmina na gliomagênese
Beneficiário:Marcela Gimenez
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 01/12898-4 - Genoma clínico
Beneficiário:Suely Kazue Nagahashi Marie
Linha de fomento: Auxílio à Pesquisa - Programa GENOMA
Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
Beneficiário:Suely Kazue Nagahashi Marie
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 11/07568-7 - Shotgun proteomics em estudos de glioma, nas interações de complexos protéicos com nucleofosmina e no proteoma/fosfoproteoma de linhagens celulares derivadas de glioblastoma multiforme (GBM) estimuladas por EGF
Beneficiário:José César Rosa
Linha de fomento: Auxílio à Pesquisa - Regular