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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01180

Master regulators of signaling pathways: An application to the analysis of gene regulation in breast cancer

 Diana Tapia-Carrillo1,  Hugo Tovar1, Tadeo Velázquez-Caldelas1 and  Enrique Hernandez-Lemus2*
  • 1Instituto Nacional de Medicina Genómica (INMEGEN), Mexico
  • 2Computational Genomics, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico

Analysis of gene regulatory networks allows the identification of Master Transcriptional Factors that control specific groups of genes. In this work we inferred a gene regulatory network from a large dataset of breast cancer samples to identify the Master Transcriptional Factors that control the genes within signal transduction pathways. The focus in a particular subset of relevant genes constitutes an extension of the original MARINa analysis.

This modified version of MARINa utilizes a restricted molecular signature containing genes from the 25 human pathways in KEGG's signal transduction category. Our breast cancer RNAseq expression data set consists of 881 samples comprising tumors and normal mammary gland tissue.

The top 10 Master Transcriptional Factors found to regulate Signal Transduction pathways in breast cancer, we identified are: TSHZ2, HOXA2, MEIS2, HOXA3, HAND2, HOXA5, TBX18, PEG3, GLI2 and CLOCK. The functional enrichment of the regulons of these Master Transcriptional Factors showed an important proportion of processes related to morphogenesis. Our results suggest that, as part of the aberrant regulation of signaling pathways in breast cancer, pathways similar to the regulation of cell differentiation, cardiovascular system development and vasculature development may be dysregulated and co-opted in favor of tumor development through the action of these transcription factors.

Keywords: breast cancer, master regulator, Signaling Pathways, Transcription Factors, development

Received: 27 May 2019; Accepted: 24 Oct 2019.

Copyright: © 2019 Tapia-Carrillo, Tovar, Velázquez-Caldelas and Hernandez-Lemus. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Enrique Hernandez-Lemus, Instituto Nacional de Medicina Genómica (INMEGEN), Computational Genomics, Mexico City, Mexico, ehernandez@inmegen.gob.mx