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

• DOI: 10.1038/s41467-018-07657-1
• Publication Date: 2018-12-03T09:43:05Z
• Authors: Andrew Dhawan; Jacob G. Scott; Adrian L. Harris; Francesca M. Buffa
• Keywords: 0301 basic medicine; 0303 health sciences; Epithelial-Mesenchymal Transition; Science; Gene Expression Profiling; Tumor Suppressor Proteins; Q; PTEN Phosphohydrolase; Down-Regulation; Membrane Proteins; Cadherins; 7. Clean energy; gene networks; mirna; cancer; Article; Cyclin-Dependent Kinases; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; 13. Climate action; Neoplasms; Humans; Gene Regulatory Networks; Cell Proliferation; Signal Transduction

AbstractmicroRNAs 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.