Study of potential mechanism of regulation of microRNAs by sphingosine kinase 2

• Grant number: 22/10740-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2022
• End date: August 31, 2027
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Andréia Machado Leopoldino
• Grantee: Thaís Moré Milan
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 16/19103-2 - SET and sphingolipids in head and neck squamous cell carcinoma: signaling, targets and antiumoral therapy, AP.TEM
• Associated scholarship(s): 23/15046-8 - Exploring the Dynamic Interplay of Sphingosine Kinase 2 and p53 in Head and Neck Carcinoma Organoids, BE.EP.DR

Abstract

Head and neck squamous cell carcinoma (HNSCC) has high incidence and recurrence rates. In addition to genomic alterations, epigenetics, such as dysregulation of microRNAs (miRNAs), also occur in HNSCC. Recently, our research group characterized the relationship of sphingolipids and sphingosine kinase 2 (SK2) with oral squamous cancer. Furthermore, the RNA sequence data showed the deregulation of several miRNAs associated with SK2, many of which are targets for p53. The present project aims to investigate the potential role of SK2 in the mechanism of transcriptional and post-transcriptional regulation of miRNAs, with the participation of p53. Different cell models will be used in vitro to identify and characterize the relationship between SK2, p53, and miRNAs, such as cell lines with overexpression and/or reduction of SK2, protein-protein and protein-DNA/RNA interaction analysis by immunoprecipitation, protein status (phosphorylation/methylation/acetylation) by Western blotting and/or immunofluorescence, 3D culture and flow cytometry to determine stem cell profiling. In vivo assays such as tumor xenograft model, will be used in nude mice. The expected results include advancing the frontier of knowledge about miRNAs/SK2/p53 and elucidating targets for the development of new strategies and therapies against oral cancer.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, GABRIEL; MILAN, THAIS MORE; LEOPOLDINO, ANDREIA MACHADO. The accumulation of sphingosine kinase 2 disrupts the DNA damage response and promotes resistance to genotoxic agents. Gene, v. 897, p. 6-pg., 2023-12-15. (18/17480-9, 22/10740-0, 16/19103-2)

MILAN, THAIS MORE; SILVA, GABRIEL; SOUSA, LUCAS OLIVEIRA; LEOPOLDINO, ANDREIA MACHADO. Sphingosine Kinase 2 Controls the Aggressive Phenotype of Oral Squamous Cell Carcinoma by Regulating miR-205 and miR-296 through p53. American Journal of Pathology, v. 195, n. 2, p. 13-pg., 2025-01-24. (16/19103-2, 23/09624-9, 22/10740-0)