MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes

Laura Cantini, Claudio Isella, Consalvo Petti, Gabriele Picco, Simone Chiola, Elisa Ficarra, Michele Caselle, Enzo Medico

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish
Article number8878
JournalNature Communications
Volume6
DOIs
Publication statusPublished - Nov 17 2015

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regulators
MicroRNAs
Colorectal Neoplasms
cancer
Messenger RNA
network analysis
gene expression
stems
interactions
signature analysis
statistical tests
prognosis
Electric network analysis
Gene expression
classifiers
cultured cells
genes
Down-Regulation
tumors
Statistical tests

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes. / Cantini, Laura; Isella, Claudio; Petti, Consalvo; Picco, Gabriele; Chiola, Simone; Ficarra, Elisa; Caselle, Michele; Medico, Enzo.

In: Nature Communications, Vol. 6, 8878, 17.11.2015.

Research output: Contribution to journalArticle

Cantini, Laura ; Isella, Claudio ; Petti, Consalvo ; Picco, Gabriele ; Chiola, Simone ; Ficarra, Elisa ; Caselle, Michele ; Medico, Enzo. / MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes. In: Nature Communications. 2015 ; Vol. 6.
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