Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of cancer death worldwide. Despite advances in therapies such as surgery, chemotherapy and radiotherapy, approximately 50% of diagnosed patients have metastases and their survival expectancy is less than 3 years. The poor prognosis of advanced CRC is due, in large part, to a lack of knowledge of the molecular mechanisms involved. In recent years, it has been shown that the development and progression of CRC are related to aberrant changes in epitranscriptomics, which refers to chemical modifications in RNA molecules that affect gene expression and, therefore, cell function.

In fact, alterations in the expression of writers, readers and erasers of m6A marks, the most common modification in RNA, have been linked to increased growth, invasion, migration, chemoresistance and metastasis in CRC. Data from our laboratory suggest that DNA topoisomerase II (TOP2), an enzyme that regulates DNA topology, is essential for the deposition of m6A in nascent mRNA. The main objective of this project is to comprehensively study the regulatory mechanisms governing m6A methylation through TOP2 activity in CRC through proteomics studies.

We plan to identify proteins involved in the regulation of m6A methylation and, subsequently, characterize their function in key cellular processes for the development of CRC. This project will allow us to understand the molecular mechanisms responsible for epitranscriptomic changes in CRC and will shed light on potential biomarkers and therapeutic targets for this type of tumor, which could lead to the development of more effective targeted therapies and diagnostic tools.