Characterization of the role of ZFHX4 in osteosarcoma cell lines

• Grant number: 25/06104-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: August 18, 2025
• End date: September 17, 2025
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Mariana Camargo Maschietto
• Grantee: Ester Fernandes Martins Rodrigues
• Supervisor: Sabrina Wurzba
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
• Institution abroad: McGill University, Canada
• Associated to the scholarship: 23/10527-8 - Characterization of telomere and associated genes in pediatric osteosarcomas, BP.IC

Abstract

Osteosarcoma is the most prevalent bone tumor of childhood and adolescence, with an annual incidence rate of 4.13 cases per million in Brazil (0-19 years). These tumors stand out for aggressive clinical courses, high propensity to metastasis detection at diagnosis, and highly unstable and complex genomes, which hampers the unraveling of the complete set of events involved in its initiation, progression, and clinical outcomes. Genomic and DNA methylation alterations of pediatric osteosarcoma identified recurrently disrupted genes and biological processes that include the DNMT3B, KNL1, TNFRSF11B and ZFHX4. Among these, the genes were involved in maintaining DNA methylation patterns, cell cycle, transcriptional regulation or skeletal system development mechanisms that could be related to osteosarcoma progression or resistance to treatment. To further explore these findings, we selected the gene ZFHX4 and we propose a collaboration with Dr. Sabrina Wurzba from McGill University, Canada, who has extensive experience in functional genomics. The proposed work plan includes (a) gene expression analysis of ZFHX4, identified by previous analyses, and (b) the establishment of cellular knock-in and knockout models of this gene using the CRISPR-Cas9 system in osteosarcoma cell lines, with further functional evaluation. Based on this collaboration, we intend to provide significant improvements in the technical-scientific training of the student, and strengthen the collected evidence for the role of this gene in osteosarcomas.