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

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.