Epigenetic regulation of 5-methylcytosine RNA modification in human cancer

Abstract

The general aim of this thesis is to identify and characterize if there are DNA methylation patterns giving rise to cancer-related m5C RNA modification defects, potentially promoting malignant transformation and tumor progression. For this aim, the following specific objectives are proposed:

1. To determine if there is any m5C RNA-related enzyme that is epigenetically lost in cancer by DNA promoter hypermethylation.

2. To select a candidate gene of interest and experimentally validate its epigenetic silencing in cancer.

3. To characterize the cellular implications of the observed epigenetic lesion in vitro, in cancer cell line models resulting from the depletion or the recovery of the enzyme of interest, and in vivo, in murine models.

4. To identify and validate target RNAs whose m5C methylation pattern is altered as a consequence of the gene of interest silencing in cancer.

5. To test whether the methylation status of the selected gene may be valuable as a biomarker in clinical management, as well as to assess its potential as putative druggable target for cancer treatment.