Identification of miRNA Master Regulators in Breast Cancer
Antonio Daniel Martínez-Gutiérrez, David Cantú de León, Oliver Millán-Catalán, Jossimar Coronel-Hernández, Alma D. Campos-Parra, Fany Iris Porras-Reyes, Angelica Exayana-Alderete, César López‐Camarillo, Nadia Jacobo‐Herrera, Rosalío Ramos‐Payán, Carlos Pérez‐Plasencia
Abstract
Breast cancer is the neoplasm with the highest number of deaths in women. Although the molecular mechanisms associated with the development of this tumor have been widely described, metastatic disease has a high mortality rate. In recent years, several studies show that microRNAs or miRNAs regulate complex processes in different biological systems including cancer. In the present work, we describe a group of 61 miRNAs consistently over-expressed in breast cancer (BC) samples that regulate the breast cancer transcriptome. By means of data mining from TCGA, miRNA and mRNA sequencing data corresponding to 1091 BC patients and 110 normal adjacent tissues were downloaded and a miRNA-mRNA network was inferred. Calculations of their oncogenic activity demonstrated that they were involved in the regulation of classical cancer pathways such as cell cycle, PI3K-AKT, DNA repair, and k-Ras signaling. Using univariate and multivariate analysis, we found that five of these miRNAs could be used as biomarkers for the prognosis of overall survival. Furthermore, we confirmed the over-expression of two of them in 56 locally advanced BC samples obtained from the histopathological archive of the National Cancer Institute of Mexico, showing concordance with our previous bioinformatic analysis.