Chasing non-existent “microRNAs” in cancer
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 em...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Oncogenesis |
| Online Access: | https://doi.org/10.1038/s41389-025-00550-9 |
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| _version_ | 1849698511634825216 |
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| author | 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 Cameron P. Bracken |
| author_facet | 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 Cameron P. Bracken |
| author_sort | Ayla Orang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-057bf79f903646c2a03b81cb44ed0af2 |
| institution | DOAJ |
| issn | 2157-9024 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Oncogenesis |
| spelling | doaj-art-057bf79f903646c2a03b81cb44ed0af22025-08-20T03:18:53ZengNature Publishing GroupOncogenesis2157-90242025-04-011411910.1038/s41389-025-00550-9Chasing non-existent “microRNAs” in cancerAyla Orang0Nicholas I. Warnock1Melodie Migault2B. Kate Dredge3Andrew G. Bert4Julie M. Bracken5Philip A. Gregory6Katherine A. Pillman7Gregory J. Goodall8Cameron P. Bracken9Centre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaCentre for Cancer Biology, an alliance of SA Pathology and University of South AustraliaAbstract 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.https://doi.org/10.1038/s41389-025-00550-9 |
| spellingShingle | 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 Cameron P. Bracken Chasing non-existent “microRNAs” in cancer Oncogenesis |
| title | Chasing non-existent “microRNAs” in cancer |
| title_full | Chasing non-existent “microRNAs” in cancer |
| title_fullStr | Chasing non-existent “microRNAs” in cancer |
| title_full_unstemmed | Chasing non-existent “microRNAs” in cancer |
| title_short | Chasing non-existent “microRNAs” in cancer |
| title_sort | chasing non existent micrornas in cancer |
| url | https://doi.org/10.1038/s41389-025-00550-9 |
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