MicroRNA–mRNA interactions underlying colorectal cancer molecular subtypes

Laura Cantini, Claudio Isella, Consalvo Petti, Gabriele Picco, Simone Chiola, Elisa Ficarra, Michele Caselle and Enzo Medico ()
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Laura Cantini: Università degli Studi di Torino
Claudio Isella: Università degli Studi di Torino
Consalvo Petti: Candiolo Cancer Institute, FPO IRCCS
Gabriele Picco: Università degli Studi di Torino
Simone Chiola: Università degli Studi di Torino
Elisa Ficarra: Politecnico di Torino
Michele Caselle: Università degli Studi di Torino
Enzo Medico: Università degli Studi di Torino

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Colorectal cancer (CRC) transcriptional subtypes have been recently identified by gene expression profiling. Here we describe an analytical pipeline, microRNA master regulator analysis (MMRA), developed to search for microRNAs potentially driving CRC subtypes. Starting from a microRNA–mRNA tumour expression data set, MMRA identifies candidate regulator microRNAs by assessing their subtype-specific expression, target enrichment in subtype mRNA signatures and network analysis-based contribution to subtype gene expression. When applied to a CRC data set of 450 samples, assigned to subtypes by 3 different transcriptional classifiers, MMRA identifies 24 candidate microRNAs, in most cases downregulated in the stem/serrated/mesenchymal (SSM) poor prognosis subtype. Functional validation in CRC cell lines confirms downregulation of the SSM subtype by miR-194, miR-200b, miR-203 and miR-429, which share target genes and pathways mediating this effect. These results show that, by combining statistical tests, target prediction and network analysis, MMRA effectively identifies microRNAs functionally associated to cancer subtypes.

Date: 2015
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DOI: 10.1038/ncomms9878

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