Author(s): Serafim, Rodolfo B. ; Cardoso, Cibele ; Di Cristofaro, Luis F. M. ; Pienna Soares, Christiane [UNESP] ; Araújo Silva, Wilson ; Espreafico, Enilza M. ; Paçó-Larson, Maria L. ; Price, Brendan D. ; Valente, Valeria [UNESP]
Date: 2020
Persistent ID: http://hdl.handle.net/11449/201592
Origin: Oasisbr
Made available in DSpace on 2020-12-12T02:36:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-05-01
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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.
Department of Cellular and Molecular Biology Ribeirão Preto Medical School University of São Paulo (USP), Avenida Bandeirantes, 3900
São Paulo State University (UNESP) School of Pharmaceutical Sciences, Rodovia Araraquara - Jaú, Km 01 - s/n, Campos Ville
Department of Genetics Ribeirão Preto Medical School University of São Paulo (USP), Avenida Bandeirantes, 3900
Center for Cell-Based Therapy-CEPID/FAPESP, Rua Tenente Catão Roxo, 2501
Center for Medical Genomics HCFMRP/USP and Center for Integrative System Biology - CISBi NAP/USP University of São Paulo
Department of Radiation Oncology Dana-Farber Cancer Institute
São Paulo State University (UNESP) School of Pharmaceutical Sciences, Rodovia Araraquara - Jaú, Km 01 - s/n, Campos Ville
