Abstract
Non-coding RNAs (ncRNAs) are a heterogeneous group of transcripts that, by definition, are not translated into proteins. Since their discovery, ncRNAs have emerged as important regulators of multiple biological functions across a range of cell types and tissues, and their dysregulation has been implicated in disease. Notably, much research has focused on the link between microRNAs (miRNAs) and human cancers, although other ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as relevant contributors to human disease. In this Review, we summarize our current understanding of the roles of miRNAs, lncRNAs and circRNAs in cancer and other major human diseases, notably cardiovascular, neurological and infectious diseases. Further, we discuss the potential use of ncRNAs as biomarkers of disease and as therapeutic targets.
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Acknowledgements
The authors dedicate this Review to Deborah Silverman and to Angelo Veronese for their passion for science and love for life, who will both be sorely missed! G.A.C. is a Felix L. Haas Endowed Professor in Basic Science. Work in G.A.C.’s laboratory is supported by National Cancer Institute (NCI) grants 1R01 CA182905-01 and 1R01CA222007-01A1, National Institute of General Medical Sciences (NIGMS) grant 1R01GM122775-01, DoD Idea Award W81XWH-21-1-0030, a Team DOD grant in Gastric Cancer W81XWH-21-1-0715, a Chronic Lymphocytic Leukaemia Moonshot Flagship project, a CLL Global Research Foundation 2019 grant, a CLL Global Research Foundation 2020 grant, a CLL Global Research Foundation 2022 grant, The G. Harold & Leila Y. Mathers Foundation, two grants from Torrey Coast Foundation and an Institutional Research Grant and Development Grant associated with Brain SPORE 2P50CA127001. The M.F. laboratory is supported by the Italian Association for Research on Cancer (AIRC) under the IG 2021-ID.25789 project.
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G.A.C. is one of the scientific founders of Ithax Pharmaceuticals. The other authors declare no competing interests.
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Related links
FuncPEP: https://bioinformatics.mdanderson.org/Supplements/FuncPEP/database.html
GENCODE: https://www.gencodegenes.org/
LncRNADisease: http://www.rnanut.net/lncrnadisease
miRBase: https://www.mirbase.org/
NIH Early Detection Research Network: https://edrn.nci.nih.gov
NONCODE: http://www.noncode.org
SPENCER: http://spencer.renlab.org
The Human MicroRNA Disease Database: http://www.cuilab.cn/hmdd
Supplementary information
Glossary
- Argonaute protein
-
(Ago protein). Interactor partner protein of small non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and small interfering RNAs (siRNAs). Ago proteins facilitate small ncRNA target binding and thereby their effector mechanisms. It was recently uncovered that miRNAs can interact with other, non-Ago proteins as well.
- Ribosomal profiling
-
A deep sequencing-based method that reveals ribosome-associated mRNAs, thereby predicting regions subjected to translation.
- Short open reading frames
-
(sORFs; also known as small ORFs). Putative protein-coding sites that are 100 nucleotides long, which were previously overlooked as non-relevant regions.
- Small-molecule inhibitors
-
Compounds smaller than 500 Da developed to target any portion of a target molecule and cause its inhibition.
- Small regulatory peptides
-
(sPEPs; also called micropeptides). Polypeptides that are encoded by short open reading frames (sORFs) and consist of fewer than 100–150 amino acids, sometimes translated from non-coding RNAs (ncRNAs).
- Sponges
-
RNA molecules such as circular RNAs (circRNAs) that can bind and sequester RNAs or proteins and thereby inhibit their effects.
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Nemeth, K., Bayraktar, R., Ferracin, M. et al. Non-coding RNAs in disease: from mechanisms to therapeutics. Nat Rev Genet 25, 211–232 (2024). https://doi.org/10.1038/s41576-023-00662-1
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DOI: https://doi.org/10.1038/s41576-023-00662-1