Pan-cancer characterisation of microRNA across cancer hallmarks reveals microRNA-mediated downregulation of tumour suppressors

microRNAs are key regulators of the human transcriptome across a number of diverse biological processes, such as development, aging and cancer, where particular miRNAs have been identified as tumour suppressive and oncogenic. In this work, we elucidate, in a comprehensive manner, across 15 epithelia...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications Vol. 9; no. 1; pp. 5228 - 13
Main Authors: Dhawan, Andrew, Scott, Jacob G., Harris, Adrian L., Buffa, Francesca M.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 07.12.2018
Nature Publishing Group
Nature Portfolio
Subjects:
38/91
45/23
45/61
631/114/2164
631/208/176/2016
631/208/212/2019
631/67/69
692/4028/67/69
Aging
Biological activity
Cadherins - genetics
Cancer
Cell Proliferation - genetics
Copy number
Cyclin-Dependent Kinases - genetics
Down-Regulation
Epithelial-Mesenchymal Transition - genetics
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene regulation
Gene Regulatory Networks
Genomes
Humanities and Social Sciences
Humans
Membrane Proteins - genetics
Methylation
MicroRNAs
MicroRNAs - genetics
miRNA
multidisciplinary
Mutation
Neoplasms - classification
Neoplasms - genetics
PTEN Phosphohydrolase - genetics
PTEN protein
Redundancy
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Signal Transduction - genetics
Suppressors
Tumor suppressor genes
Tumor Suppressor Proteins - genetics
Tumors
ISSN:2041-1723, 2041-1723
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:microRNAs are key regulators of the human transcriptome across a number of diverse biological processes, such as development, aging and cancer, where particular miRNAs have been identified as tumour suppressive and oncogenic. In this work, we elucidate, in a comprehensive manner, across 15 epithelial cancer types comprising 7316 clinical samples from the Cancer Genome Atlas, the association of miRNA expression and target regulation with the phenotypic hallmarks of cancer. Utilising penalised regression techniques to integrate transcriptomic, methylation and mutation data, we find evidence for a complex map of interactions underlying the relationship of miRNA regulation and the hallmarks of cancer. This highlighted high redundancy for the oncomiR-1 cluster of oncogenic miRNAs, in particular hsa-miR-17-5p. In addition, we reveal extensive miRNA regulation of tumour suppressor genes such as PTEN, FAT4 and CDK12, uncovering an alternative mechanism of repression in the absence of mutation, methylation or copy number changes. miRNAs have emerged as regulators of diverse biological processes including cancer. Here the authors present an extended pan-cancer analysis of the miRNAs in 15 epithelial cancers; integrating methylation, transcriptomic and mutation data they reveal alternative mechanisms of tumour suppressors’ regulation in absence of mutation, methylation or copy number alterations.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-07657-1