Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer

Tommaso Mazza, Gianluigi Mazzoccoli, Caterina Fusilli, Daniele Capocefalo, Anna Panza, Tommaso Biagini, Stefano Castellana, Annamaria Gentile, Angelo De Cata, Orazio Palumbo, Raffaella Stallone, Rosa Rubino, Massimo Carella, Ada Piepoli

Research output: Contribution to journalArticle

Abstract

Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA-miRNA and miRNA-miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non-tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional backbone was fulfilled by tight micro-societies of miRNAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signaling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA-RNA crosstalk, which mechanistically modulates several signaling pathways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis.

Original languageEnglish
Pages (from-to)4025-4036
Number of pages12
JournalNucleic Acids Research
Volume44
Issue number9
DOIs
Publication statusPublished - May 19 2016

ASJC Scopus subject areas

  • Genetics

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