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

Abstract:

: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.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Serafim RB,Cardoso C,Di Cristofaro LFM,Pienna Soares C,Araújo Silva W Jr,Espreafico EM,Paçó-Larson ML,Price BD,Valente V

doi

10.1038/s41417-019-0103-0

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

319-329

issue

5

eissn

0929-1903

issn

1476-5500

pii

10.1038/s41417-019-0103-0

journal_volume

27

pub_type

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