Chasing non-existent "microRNAs" in cancer
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(Published version)
Date
2025
Authors
Orang, A.
Warnock, N.I.
Migault, M.
Dredge, B.K.
Bert, A.G.
Bracken, J.M.
Gregory, P.A.
Pillman, K.A.
Goodall, G.J.
Bracken, C.P.
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Journal article
Citation
Oncogenesis, 2025; 14(1, article no. 10):10-1-10-9
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Ayla Orang, Nicholas I. Warnock, Melodie Migault, B. Kate Dredge, Andrew G. Bert, Julie M. Bracken, Philip A. Gregory, Katherine A. Pillman, Gregory J. Goodall, and Cameron P. Bracken
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Abstract
MicroRNAs (miRNAs) are important regulators of gene expression whose dysregulation is widely linked to tumourigenesis, tumour progression and Epithelial-Mesenchymal Transition (EMT), a developmental process that promotes metastasis when inappropriately activated. However, controversy has emerged regarding how many functional miRNAs are encoded in the genome, and to what extent non-regulatory products of RNA degradation have been mis-identified as miRNAs. Central to miRNA function is their capacity to associate with an Argonaute (AGO) protein and form an RNA-Induced Silencing Complex (RISC), which mediates target mRNA suppression. We report that numerous "miRNAs" previously reported in EMT and cancer contexts, are not incorporated into RISC and are not capable of endogenously silencing target genes, despite the fact that hundreds of publications in the cancer field describe their roles. Apparent function can be driven through the expression of artificial miRNA mimics which is not necessarily reflective of any endogenous gene regulatory function. We present biochemical and bioinformatic criteria that can be used to distinguish functional miRNAs from mistakenly annotated RNA fragments.
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Data source: supplementary information, https://doi.org/10.1038/s41389-025-00550-9
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© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/.