MicroRNA–mRNA interactions underlying colorectal cancer molecular subtypes

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 ex...

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Bibliographic Details
Published in:Nature communications 2015-11, Vol.6 (1), p.8878-8878, Article 8878
Main Authors: Cantini, Laura, Isella, Claudio, Petti, Consalvo, Picco, Gabriele, Chiola, Simone, Ficarra, Elisa, Caselle, Michele, Medico, Enzo
Format: Article
Language:English
Subjects:
38/39
38/91
631/1647/48
631/208/191/2018
631/337/384/331
631/67/1504/1885
Colorectal cancer
Datasets
Gene expression
Humanities and Social Sciences
MicroRNAs
multidisciplinary
Science
Science (multidisciplinary)
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Summary: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. Colorectal cancer subtypes can be distinguished by their different biological and molecular properties. Here the authors present microRNA Master Regulator Analysis, a tool to identify microRNAs driving subtype-specific gene expression and cancer variation.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms9878