MicroRNA expression profiling and its association with chemotherapeutic drug response in colon cancer cell lines

Abstract

Colorectal cancer is among the three major causes of death by cancer worldwide. The diagnosis is made by histopathological analyses, which are used to define the tumor stages. The treatment is carried out based on the observed tumor stage. For more advanced cases (stages III and IV), it is recommended surgical excision combined with adjuvant chemotherapy. However, colorectal cancer is a disease of high genetic heterogeneity. The clinical response of patients undergoing adjuvant therapy is extremely variable, making it problematic to delineate the proper treatment. Therefore, it is essentially important to understand the mechanisms involved in chemoresistance and tumor progression, so that diagnosis and treatment may be more customized and effective.MicroRNAs are non-coding RNAs that regulate a number of cellular processes. Several studies have shown that changes in microRNA expression levels directly influence chemoresistance and tumorigenesis, serving as molecular markers. Given the potential of microRNAs as regulators of global gene expression, this project aims to investigate, by using next generation sequencing and bioinformatics approaches, the expression profile of microRNAs and its association with response to different antitumor drugs previoulsy tested in colon cancer cell lines. To this end, appropriate methods will be developed for the identification of known microRNAs and possibly characterize new molecules. We will also investigate the target genes of microRNAs, aiming to unravel regulatory mechanisms involved in resistance and sensitivity to antitumor compounds and factors that act in the tumorigenesis of colon cancer. (AU)