HJURP knockdown disrupts clonogenic capacity and increases radiation-induced cell death of glioblastoma cells.

Serafim, Rodolfo B; Cardoso, Cibele; Di Cristofaro, Luis F M; Pienna Soares, Christiane; Araújo Silva, Wilson; Espreafico, Enilza M; Paçó-Larson, Maria L; Price, Brendan D; Valente, Valeria

Serafim, Rodolfo B; Cardoso, Cibele; Di Cristofaro, Luis F M; Pienna Soares, Christiane; Araújo Silva, Wilson; Espreafico, Enilza M; Paçó-Larson, Maria L; Price, Brendan D; Valente, Valeria.

Afiliación

Serafim RB; Department of Cellular and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo (USP), Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil.
Cardoso C; Department of Cellular and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo (USP), Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil.
Di Cristofaro LFM; Department of Cellular and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo (USP), Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil.
Pienna Soares C; São Paulo State University (UNESP), School of Pharmaceutical Sciences,, Rodovia Araraquara - Jaú, Km 01 - s/n, Campos Ville, Araraquara, SP, 14800-903, Brazil.
Araújo Silva W; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo (USP), Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil.
Espreafico EM; Center for Cell-Based Therapy-CEPID/FAPESP, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, 14051-140, Brazil.
Paçó-Larson ML; Center for Medical Genomics, HCFMRP/USP, and Center for Integrative System Biology - CISBi NAP/USP, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Price BD; Department of Cellular and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo (USP), Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil.
Valente V; Department of Cellular and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo (USP), Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil.

Cancer Gene Ther ; 27(5): 319-329, 2020 05.

Article en En | MEDLINE | ID: mdl-31138900

RESUMEN

The Holliday Junction-Recognition Protein (HJURP) was reported as overexpressed in several cancers and also strongly correlated with poor prognosis of patients, especially in glioblastoma (GBM), the most common and deadly type of primary brain tumor. HJURP is responsible for loading the histone H3 variant-the Centromeric Protein A (CENP-A)-at the centromeres in a cell cycle-regulated manner, being required for proper chromosome segregation. Here we investigated HJURP association with survival and radioresistance of different GBM cell lines. HJURP knockdown compromised the clonogenic capacity and severely impaired survival of five distinct GBM cells, while nontumor astrocytes were not affected. U251MG cells showed a robust cell cycle arrest in G2/M phases followed by a drastic increment in cell death after HJURP silencing, while U138MG and U343MG cell lines presented augmented senescence with a comparable increase in cell death. Importantly, we verified that the impact on cell cycle dynamics and clonogenic survival were associated with loss CENP-A at the centromeres. Moreover, radiation resistance was also impacted by HJURP modulation in several GBM cell lines. U87MG, T98G, U138MG, and U343MG cells were all sensitized to ionizing radiation after HJURP reduction. These data reinforce the requirement of HJURP for proliferative capacity and radioresistance of tumor cells, underlining its potential as a promising therapeutic target for GBM.

Asunto(s)

Neoplasias Encefálicas/radioterapia; Proteína A Centromérica/metabolismo; Proteínas de Unión al ADN/metabolismo; Glioblastoma/radioterapia; Células Madre Neoplásicas/efectos de la radiación; Neoplasias Encefálicas/patología; Puntos de Control del Ciclo Celular/genética; Puntos de Control del Ciclo Celular/efectos de la radiación; Línea Celular Tumoral; Proliferación Celular/genética; Proliferación Celular/efectos de la radiación; Supervivencia Celular/genética; Supervivencia Celular/efectos de la radiación; Centrómero/metabolismo; Centrómero/efectos de la radiación; Proteínas de Unión al ADN/genética; Técnicas de Silenciamiento del Gen; Glioblastoma/patología; Humanos; Células Madre Neoplásicas/patología; Tolerancia a Radiación/genética; Ensayo de Tumor de Célula Madre

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Neoplásicas / Neoplasias Encefálicas / Glioblastoma / Proteínas de Unión al ADN / Proteína A Centromérica Límite: Humans Idioma: En Revista: Cancer Gene Ther Asunto de la revista: GENETICA MEDICA / NEOPLASIAS / TERAPEUTICA Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido

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