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MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes.


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.

SUBMITTER: Cantini L 

PROVIDER: S-EPMC4660217 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes.

Cantini Laura L   Isella Claudio C   Petti Consalvo C   Picco Gabriele G   Chiola Simone S   Ficarra Elisa E   Caselle Michele M   Medico Enzo E  

Nature communications 20151117


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  ...[more]

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