A miR-335/COX-2/PTEN axis regulates the secretory phenotype of senescent cancer-associated fibroblasts
Open accessAbstract
Senescent cancer-associated fibroblasts (CAF) develop a senescence-associated secretory phenotype (SASP) that is believed to contribute to cancer progression. The mechanisms underlying SASP development are, however, poorly understood. Here we examined the functional role of microRNA in the development of the SASP in normal fibroblasts and CAF. We identified a microRNA, miR-335, up-regulated in the senescent normal fibroblasts and CAF and able to modulate the secretion of SASP factors and induce cancer cell motility in co-cultures, at least in part by suppressing the expression of phosphatase and tensin homologue (PTEN). Additionally, elevated levels of cyclo-oxygenase 2 (PTGS2; COX-2) and prostaglandin E2 (PGE2) secretion were observed in senescent fibroblasts, and inhibition of COX-2 by celecoxib reduced the expression of miR-335, restored PTEN expression and decreased the pro-tumourigenic effects of the SASP. Collectively these data demonstrate the existence of a novel miRNA/PTEN-regulated pathway modulating the inflammasome in senescent fibroblasts.
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Senescent cells are known to make prostaglandin E2.
“Senescent cells are known to produce prostaglandin E2 (PGE2) (Cormenier et al., 2018; Dagouassat et al., 2013; Kabir et al., 2016; Martien et al., 2013; Yang et al., 2011; Zdanov et al., 2007)”
From Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis (2021) · cites this paper as Kabir et al., 2016
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References 46 · Cited by 78
Research works printed but not linked: 1
- [39]White ES Atrasz RG Hu B Phan SH Stambolic V Mak TW Hogaboam CM Flaherty KR Martinez FJ Kontos CD Toews GB Negative regulation of myofibroblast differentiation by PTEN Phosphatase and Tensin Homolog Deleted on chromosome 10 Am J Respir Crit Care Med 2006 173 112 21 16179636 PMC1434700
- Authors
- Kabir, T. D., Leigh, R. J., Tasena, H., Mellone, M., Coletta, R. D., Parkinson, E. K., Prime, S. S., Thomas, G. J., Paterson, I. C., Zhou, D., McCall, J., Speight, P. M., & Lambert, D. W.
- Affiliations
- Dunedin Public Hospital (NZ)
- University of Sheffield (GB)
- University of Southampton (GB)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Queen Mary University of London (GB)
- University of Malaya (MY)
- University of Otago (NZ)
- Corresponding author
- Lambert, Daniel W.
- ORCID
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2016-06-29
- Volume
- 8
- Issue
- 8
- Pages
- 1608-1635
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC5032686
- OpenAlex
- W2471558537
- Cited by
- 78
- References
- 46
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 12 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 12 · 2016: 2
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- ePrints Soton (University of Southampton) (acceptedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- Funders
- University of Otago
- Universiti Malaya
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- miR-335, senescence-associated secretory phenotype, cancer-associated fibroblasts, PTEN, cyclooxygenase-2, prostaglandin E2, celecoxib, microRNA, fibroblast senescence, tumor cell motility, inflammasome, tumor microenvironment
- MeSH terms
- Celecoxib, Cancer-Associated Fibroblasts, Cell Movement, Humans, Phenotype, Dinoprostone, Signal Transduction, Up-Regulation, Cellular Senescence, Coculture Techniques, MicroRNAs, PTEN Phosphohydrolase, Cyclooxygenase 2
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