The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition
Open accessAbstract
Background: MicroRNAs are modifiers of gene expression, acting to reduce translation through either translational repression or mRNA cleavage. Recently, it has been shown that some microRNAs can act to promote or suppress cell transformation, with miR-17-92 described as the first oncogenic microRNA. The association of miR-17-92 encoded microRNAs with a surprisingly broad range of cancers not only underlines the clinical significance of this locus, but also suggests that miR-17-92 may regulate fundamental biological processes, and for these reasons miR-17-92 has been considered as a therapeutic target. Results: In this study, we show that miR-17-92 is a cell cycle regulated locus, and ectopic expression of a single microRNA (miR-17-5p) is sufficient to drive a proliferative signal in HEK293T cells. For the first time, we reveal the mechanism behind this response - miR-17-5p acts specifically at the G1/S-phase cell cycle boundary, by targeting more than 20 genes involved in the transition between these phases. While both pro- and anti-proliferative genes are targeted by miR-17-5p, pro-proliferative mRNAs are specifically up-regulated by secondary and/or tertiary effects in HEK293T cells. Conclusion: The miR-17-5p microRNA is able to act as both an oncogene and a tumor suppressor in different cellular contexts; our model of competing positive and negative signals can explain both of these activities. The coordinated suppression of proliferation-inhibitors allows miR-17-5p to efficiently de-couple negative regulators of the MAPK (mitogen activated protein kinase) signaling cascade, promoting growth in HEK293T cells. Additionally, we have demonstrated the utility of a systems biology approach as a unique and rapid approach to uncover microRNA function.
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The most abundant miRNA was miR-17-5p, while miR-20a-5p, miR-92a-5p, miR-19b-3p, miR-18a-5p, and miR-19a-3p were second through sixth most abundant.
“the most abundant miRNA was miR-17-5p, which has previously been shown to regulate cell cycle progression in 293T cells (Cloonan et al., 2008), while miR-20a-5p, miR-92a-5p, miR-19b-3p, miR-18a-5p, and miR-19a-3p were second through sixth most abundant.”
From Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP (2022) · cites this paper as Cloonan et al., 2008
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- Authors
- Cloonan, N., Brown, M. K., Steptoe, A. L., Wani, S., Chan, W. L., Forrest, A. R., Kolle, G., Gabrielli, B., & Grimmond, S. M.
- Affiliations
- The University of Queensland (AU)
- Princess Alexandra Hospital (AU)
- Corresponding author
- Grimmond, Sean M
- Venue
- Genome Biology
- Published
- 2008-08-14
- Volume
- 9
- Issue
- 8
- Pages
- R127-R127
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC2575517
- OpenAlex
- W2108836814
- Cited by
- 304
- References
- 39
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 12 · 2022: 18 · 2021: 15 · 2020: 21 · 2019: 14 · 2018: 19 · 2017: 12 · 2016: 11 · 2015: 19 · 2014: 24 · 2013: 27 · 2012: 25
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Griffith Research Online (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council (456140)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- miR-17-5p, miR-17-92 cluster, microRNA, G1/S transition, cell cycle regulation, oncogenic microRNA, tumor suppressor, MAPK signaling, cell proliferation, HEK293T cells, systems biology, miRNA target genes
- MeSH terms
- Cell Line, Humans, RNA, Messenger, Protein Biosynthesis, Signal Transduction, G1 Phase, S Phase, MicroRNAs, Mitogen-Activated Protein Kinase 9, Cell Proliferation
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