Pan-cancer characterisation of microRNA with hallmarks of cancer reveals role of microRNA-mediated downregulation of tumour suppressor genes [article]

Andrew Dhawan, Jacob G Scott, Adrian L Harris, Francesca M Buffa
2017 bioRxiv   pre-print
microRNA are key regulators of the human transcriptome across a number of diverse biological processes, such as development, aging, and cancer, where particular miRNA have been identified as tumour suppressive and oncogenic. In this work, we sought to elucidate, in a comprehensive manner, across 15 epithelial cancer types comprising 7,316 clinical samples from the Cancer Genome Atlas, the association of miRNA expression and target regulation with the phenotypic hallmarks of cancer. Utilising
more » ... alized 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.
doi:10.1101/238675 fatcat:jul3j3mblzejxobv3t3jqecpuy