Regulation of the cell cycle in cancer cells by RNA methylation.
Our research group is interested in discovering the molecular mechanisms that regulate the function of stem cells in the maintenance of adult tissues, as well as discovering the altered molecular mechanisms in common pathologies such as cancer or multiple sclerosis and in rare diseases. In particular, we seek to understand the pathophysiological role of the epitranscriptome or RNA modifications in cancer and other diseases. Covalent chemical modifications of RNA are beginning to define a new layer of biological complexity that is being widely appreciated as the epitranscriptome. More than 170 covalent chemical modifications are known and whose function is still unknown. The most recent evidence reveals that some of these post-transcriptional modifications mediate the regulation of self-renewal or survival processes and mediate or modulate gene expression and the efficiency and precision of protein translation. Our findings show that RNA methylation regulates self-renewal processes and stress response of tumor-initiating cells. We also demonstrate that manipulation of these pathways specifically sensitizes cancer stem cells to chemotherapeutic agents. Based on these findings, we propose the study of post-transcriptional modifications as new ways to identify anti-tumor therapeutic strategies.
The research and training project of the ERASMUS student aims to understand the molecular mechanisms underlying the epitranscriptome in prostate cancer and specifically the role of NSUN5 RNA methylase in the regulation of the cell cycle and to determine the therapeutic potential of the genetic manipulation of NSUN5 in cell cultures and in in vivo mouse models of prostate cancer. For this we use a combination of molecular and cellular biology techniques, cellular models (CRISPR), murine models (xenografts and transgenic mice) and samples from patients or cancer expression databases such as TCGA.