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Analysis of the impact of HJURP silencing on the control of replicative stress in GBM cells

Grant number: 17/03102-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2017
Effective date (End): December 31, 2018
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Valeria Valente
Grantee:Enzo Alexandre Kuratomi
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

Astrocytomas are the most common primary brain tumors in adults and are classified as low grade diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (grade IV). Glioblastoma multiforme (GBM), the most common and lethal primary brain tumor in adults, is characterized by high invasiveness and resistance to radio and chemotherapy. The Holliday Junction-Recognizing Protein (HJURP) protein is highly expressed in GBM cases and our studies have pointed out that HJURP is involved in DNA repair, chromosomal stability and segregation, and modulation of mechanisms of apoptosis and senescence. Research from our laboratory has shown that HJURP superexpressor cells have a higher rate of proliferation and clonogenic capacity and lower replicative stress. On the other hand, the reduction of HJURP promoted increased levels of apoptosis in GBM cell lines, whereas non-tumor cells were not significantly affected. The objective of the research is to verify the impact of HJURP silencing on the capacity of proliferation and maintenance of replicative stress in GBM cells. For this, we will analyze cell lines expressing a short hairpin RNA (shRNA) directed to HJURP and determined the proliferation curve, the levels of HJURP expression and the quantification of the activation of RPA (replicative stress marker) and DNA double strand breaks after treatment with camptothecin, a drug that inhibits topoisomerase and causes replicative stress.