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Cited by 308MicroRNA in disease regulationCancer-related Molecular PathwaysCancer-related molecular mechanisms research

microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells

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Wang, Peng, Zou, Fangdong, Zhang, Xiaodong, Li, Hua, Dulak, Austin, Tomko, Robert J., Lazo, John S., Wang, Zhenghe, Zhang, Lin, Yu, Jian·2009·Cancer Research
DOI 10.1158/0008-5472.can-09-1996PMC PMC2763324

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Abstract

microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain insights into its potential role in tumorigenesis, we generated miR-21 knockout colon cancer cells through gene targeting. Unbiased microarray analysis combined with bioinformatics identified cell cycle regulator Cdc25A as a miR-21 target. miR-21 suppressed Cdc25A expression through a defined sequence in its 3′-untranslated region. We found that miR-21 is induced by serum starvation and DNA damage, negatively regulates G1-S transition, and participates in DNA damage–induced G2-M checkpoint through down-regulation of Cdc25A. In contrast, miR-21 deficiency did not affect apoptosis induced by a variety of commonly used anticancer agents or cell proliferation under normal cell culture conditions. Furthermore, miR-21 was found to be underexpressed in a subset of Cdc25A-overexpressing colon cancers. Our data show a role of miR-21 in modulating cell cycle progression following stress, providing a novel mechanism of Cdc25A regulation and a potential explanation of miR-21 in tumorigenesis. [Cancer Res 2009;69(20):8157–65]

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  • Targeted deletion of miR-21 in RKO and DLD1 colon cancer cells revealed miR-21 contributes to tumorigenesis through compromising cell cycle progression and DNA damage-induced checkpoint function through the Cdc25a target gene.

    “Targeted deletion of miR-21 in RKO and DLD1 colon cancer cells revealed miR-21 contributes to tumorigenesis through compromising cell cycle progression and DNA damage-induced checkpoint function through the Cdc25a target gene (Wang et al., 2009).”

    From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Wang et al., 2009

    The Results report targeted miR-21 deletion in RKO and DLD1 cells, and the Discussion links miR-21, Cdc25A, cell-cycle progression, and checkpoint activation. However, the Discussion describes a contribution to tumorigenesis as a possibility, not a demonstrated outcome; the claim's “revealed” overstates that conclusion. (LLM, conf=0.88)

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References 51 · Cited by 308

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Authors
Wang, P., Zou, F., Zhang, X., Li, H., Dulak, A., Tomko, R. J., Lazo, J. S., Wang, Z., Zhang, L., & Yu, J.
Affiliations
  • University of Pittsburgh (US)
  • Case Comprehensive Cancer Center (US)
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2009-10-14
Volume
69
Issue
20
Pages
8157-8165
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-09-1996
PMC
PMC2763324
OpenAlex
W2052487210
Cited by
308
References
51
Citations by year
2025: 9 · 2024: 9 · 2023: 9 · 2022: 10 · 2021: 15 · 2020: 14 · 2019: 9 · 2018: 9 · 2017: 17 · 2016: 21 · 2015: 28 · 2014: 36 · 2013: 34 · 2012: 31
FWCI
9.84
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R01CA106348, R01CA127590, R01CA129829, R01CA121105, U54CA116867)
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-21, CDC25A, colon cancer, cell cycle progression, G1/S transition, G2/M checkpoint, DNA damage response, serum deprivation, 3' untranslated region, carcinogenesis, apoptosis, cell proliferation
MeSH terms
Bromodeoxyuridine, Cell Cycle, DNA Damage, Humans, Luciferases, Mitotic Index, RNA, Messenger, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, cdc25 Phosphatases, Gene Expression Profiling, RNA, Small Interfering, MicroRNAs, Cell Proliferation

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