Expression of RNA modifying enzymes in clear cell renal cell carcinoma and breast adenocarcinoma

• Grant number: 18/15493-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2019
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Glaucia Noeli Maroso Hajj
• Grantee: Fernanda Ferreira da Silva
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Epigenetic modifications are covalent chemical alterations that may occur in DNA or RNA molecules, but without sequence alteration. Currently, it has been known the modifications of ribosomal, transporter, and messenger RNAs. The first acknowledged mRNA modification was the N6-metiladenosine (m6A) it being followed afterwards by the discovering of pseudouridine (¨), 5-metilcitidine (5mC) and N1-metiladenosine (m1A). The RNA modifications affect almost all stages of RNA's metabolism, since the processing in the nucleus until the translation and decay in the cytoplasm, altering gene expression levels. The proteins which add modifications to RNA are named "writers", the enzymes which remove the modifications are named "erasers" and the proteins which identify the modifications are named "readers". Thus, considering that mRNA epigenetic modifications may regulate gene expression at several levels, it is expected that alterations in these mechanisms can influence the emergence of various pathologies, for instance, cancer. Data from TCGA imply that in some types of tumors, as clear cell renal cell carcinoma (CCRCC) and breast adenocarcinoma, may occur an unbalance in RNA modifying enzymes expression. Therefore, it is possible that in these tumor types these alterations may cause a huge impact in gene expression levels and influence several clinical and biological aspects. This project aim to determine the expression levels of RNA modifying enzymes, m6A levels and its correlation with clinical and histopathological data for CRCC and breast adenocarcinoma, which could help us expand knowledge about molecular mechanisms associated with these diseases. (AU)