Profile of epigenetic modifications of histones and their regulators in tumor stem cells (TCCs) and exosomes in oral Carcinoma cell lines

• Grant number: 21/13268-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2022
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Luciana Oliveira de Almeida
• Grantee: Lucas Dias de Oliveira
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/11780-8 - Study of epigenetic modifications related to cancer stem cells accumulation in head and neck cancer: implications in chemoresistance, AP.JP

Abstract

Oral carcinoma is responsible for many deaths each year and has a great capacity to develop recurrences and metastases due to failures in therapy associated with chemoresistance. Conventional treatments such as radio and chemotherapy destroy differentiated tumor cells, but a small population called tumor stem cells remain intact and repopulate the tumor. These treatments favor the increase and accumulation of tumor stem cells as they are able to maintain a quiescent state that escapes therapeutic targets, causing tumor recurrence due to the origin of new cells in different states of plasticity and tumorigenicity. There are several ways used by these cells such as controlling the transcriptional machinery, changing the behavior and expression levels of genes, without changing the DNA sequence, such as DNA methylation, histone acetylation and methylation. In addition to expression and translation pathways, tumor stem cells are capable of producing extracellular vesicles known as exosomes, which are transport vehicles that favor the biological process of intercellular communication. It is believed that these particles are directly involved in the tumorigenesis process, supporting the development and progression of tumors. The exosome cargo is composed of proteins, lipids, non-coding RNAs and messenger RNA (mRNA). This cargo is responsible for allowing epigenetic and metabolic changes in recipient cells, leading to the development and progression of tumors. Therefore, a better understanding of the most active epigenetic mechanisms in tumor stem cells may support the development of more specific therapeutic targets, reducing tumor resistance and complete eradication of cells from the tumor microenvironment. This project will seek to identify differences in the regulation of the epigenetic machinery, with an emphasis on acetylation and methylation of histones and their modifying enzymes, and in the production and content of exosomes between tumor stem cell and non-tumor stem cell populations of oral carcinoma cell lines. (AU)