miR-124-2, miR-92-A1 and miR-372 regulate differential gene expression in a mathematical model of the progression of ductal carcinoma in situ (DCIS) to microinvasive breast cancer (MIBC)

Abstract

Breast cancer is a widely studied genetic disease that has a clear division between an initial stage, starting with the atypical ductal hyperplasia progressing to ductal carcinoma in situ and ending, although not necessarily, with invasive breast cancer. Nonetheless, if the invasive breast cancer has only colonized less than 1mm of healthy estroma it is classified as microinvasive breast carcinoma. We hypothesized that differentially expressed genes in tumoral cells of early carcinoma are regulated by specific miRNAs and TF that stimulate the progression to an invasive stage. Our main goal was to reach a minimal model that can explain this behavior and identify promising miRNA targets with therapeutic potential. Using BioNetUCR and COPASI for a systems biology approach, we identified miRNAs miR-372, miR-124-2 and miR-92-A1 that modify the differential gene expression in MIBC stage. These miRNAs have potential as therapeutic targets for future treatment strategies by suppressing the transition from DCIS to IBC. There are few studies about DCIS to MIBC transition, but with this computational approach we present one of the first in silico models for this type of cell transition.