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Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth
Open accessAbstract
The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers including squamous cell carcinoma of the head and neck (SCCHN). Previous investigations have demonstrated that activated Stat3 contributes to a loss of growth control and transformation. To investigate the therapeutic potential of blocking Stat3 in cancer cells, we developed a transcription factor decoy to selectively abrogate activated Stat3. The Stat3 decoy was composed of a 15-mer double-stranded oligonucleotide, which corresponded closely to the Stat3 response element within the c-fos promoter. The Stat3 decoy bound specifically to activated Stat3 and blocked binding of Stat3 to a radiolabeled Stat3 binding element. By contrast, a mutated version of the decoy that differed by only a single base pair did not bind the activated Stat3 protein. Treatment of head and neck cancer cells with the Stat3 decoy inhibited proliferation and Stat3-mediated gene expression, but did not decrease the proliferation of normal oral keratinocytes. Thus, disruption of activated Stat3 by using a transcription factor decoy approach may serve as a novel therapeutic strategy for cancers characterized by constitutive Stat3 activation.
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“Nucleic acid–based drugs, including decoy oligonucleotides and, perhaps, G-quartet oligonucleotides, have been identified that inhibit STAT3-mediated gene expression and inhibit growth of different cancer cell lines (Leong et al., 2003; Lewis et al., 2008; Sun et al., 2008; Shen et al., 2009; Zhang et al., 2013b; Liu et al., 2014; Sen et al., 2014).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Leong et al., 2003
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Metadata
- Authors
- Leong, P. L., Andrews, G. A., Johnson, D. E., Dyer, K. F., Xi, S., Mai, J. C., Robbins, P. D., Gadiparthi, S., Burke, N. A., Watkins, S. F., & Grandis, J. R.
- Affiliations
- University of Pittsburgh (US)
- Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-03-14
- Volume
- 100
- Issue
- 7
- Pages
- 4138-4143
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC153061
- OpenAlex
- W2143812692
- Cited by
- 340
- References
- 47
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 13 · 2023: 11 · 2022: 6 · 2021: 8 · 2020: 13 · 2019: 14 · 2018: 10 · 2017: 3 · 2016: 8 · 2015: 20 · 2014: 16 · 2013: 23 · 2012: 25
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Academy of Otolaryngology-Head and Neck Surgery
- National Institutes of Health
- National Cancer Institute (CA77308, R01CA077308)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- STAT3, transcription factor decoy, head and neck squamous cell carcinoma, c-fos promoter, constitutive STAT3 activation, tumor cell proliferation, oral keratinocytes
- MeSH terms
- Carcinoma, Squamous Cell, Cell Division, DNA-Binding Proteins, Head and Neck Neoplasms, Humans, Luciferases, Tumor Cells, Cultured, Trans-Activators, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Oligodeoxyribonucleotides, Antisense, STAT3 Transcription Factor, bcl-X Protein
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