Cited by 305MicroRNA in disease regulationCancer-related Molecular PathwaysCancer-related molecular mechanisms research

The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition

Open access
Cloonan, Nicole, Brown, Mellissa K, Steptoe, Anita L, Wani, Shivangi, Chan, Wei Ling, Forrest, Alistair RR, Kolle, Gabriel, Gabrielli, Brian +1 more·2008·Genome Biology

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/gb-2008-9-8-r127

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

2 of the 39 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

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
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review