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...

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Veröffentlicht in:	Nature communications Jg. 9; H. 1; S. 5228 - 13
Hauptverfasser:	Dhawan, Andrew, Scott, Jacob G., Harris, Adrian L., Buffa, Francesca M.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 07.12.2018 Nature Publishing Group Nature Portfolio
Schlagworte:	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
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Abstract	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.
AbstractList	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.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. 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. 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. 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.
ArticleNumber	5228
Author	Dhawan, Andrew Scott, Jacob G. Harris, Adrian L. Buffa, Francesca M.
Author_xml	– sequence: 1 givenname: Andrew orcidid: 0000-0002-5027-1277 surname: Dhawan fullname: Dhawan, Andrew organization: Department of Oncology, Medical Sciences Division, University of Oxford – sequence: 2 givenname: Jacob G. orcidid: 0000-0003-2971-7673 surname: Scott fullname: Scott, Jacob G. organization: Translational Hematology and Radiology, Cleveland Clinic – sequence: 3 givenname: Adrian L. surname: Harris fullname: Harris, Adrian L. organization: Department of Oncology, Medical Sciences Division, University of Oxford – sequence: 4 givenname: Francesca M. orcidid: 0000-0003-0409-406X surname: Buffa fullname: Buffa, Francesca M. email: francesca.buffa@oncology.ox.ac.uk organization: Department of Oncology, Medical Sciences Division, University of Oxford
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Snippet	microRNAs are key regulators of the human transcriptome across a number of diverse biological processes, such as development, aging and cancer, where... miRNAs have emerged as regulators of diverse biological processes including cancer. Here the authors present an extended pan-cancer analysis of the miRNAs in...
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SubjectTerms	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
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Title	Pan-cancer characterisation of microRNA across cancer hallmarks reveals microRNA-mediated downregulation of tumour suppressors
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