Supervisore: Prof. Tell

Role of APE1 and its interactome in the regulation of genotoxicant-related miRNAs involved in chemoresistance

MicroRNAs (miRNAs) play important roles in gene expression regulation at the post-transcriptional level, and their imbalance is implicated in several human diseases, including cancer. Indeed, changes in miRNAs levels can have important functions in carcinogenesis through cancer gene expression alteration, particularly in association with chemoresistance mechanisms involving genotoxic treatments. Therefore, miRNAs have recently emerged as novel biomarkers for diagnosis, prognosis, and prediction of drug response for several malignancies and they represent as well novel targets for therapeutic intervention.
However, the molecular processes regulating miRNAs expression, turnover and quality control are still poorly known. Recently, the human apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), canonically involved in the Base Excision Repair (BER) pathway of DNA lesions, has emerged as a promising cancer biomarker and a novel target for cancer treatments also for its unpredicted functions in miRNA biogenesis and exosomal sorting, with several lines of evidence confirming the involvement of APE1 interactome in these pathways. The current project is aimed at identifying miRNAs involved in chemoresistance processes whose biogenesis and/or secretion is regulated by APE1, highlighting the possibility of using APE1 inhibitors to enhance the efficacy of cancer treatments in patients with specific miRNA signatures.