ArticleJournal of experimental & clinical cancer research : CR2021
Targeted eicosanoids profiling reveals a prostaglandin reprogramming in breast Cancer by microRNA-155.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 24 citations in OpenAlex.
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- Role and Significance of MicroRNAs in the Relationship Between Obesity and Cancer.Balkan medical journal · 2025Review
- Comprehensive analysis of metabolic patterns in renal cell carcinoma: implications for prognosis and treatment.Frontiers in immunology · 2025Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Advances in PGD2/PTGDR2 signaling pathway in tumors: A review.Biomolecules & biomedicine · 2024Review
- Prostaglandin analogues signal detection by data mining in the FDA Adverse Event Reporting System database.BMJ open ophthalmology · 2024Article
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- PTGES Expression Is Associated with Metabolic and Immune Reprogramming in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Article
- The Role of Different Types of microRNA in the Pathogenesis of Breast and Prostate Cancer.International journal of molecular sciences · 2023Review
- Obesity as a Risk Factor for Breast Cancer-The Role of miRNA.International journal of molecular sciences · 2022Review
- Interleukin-4 treatment reduces leukemia burden in acute myeloid leukemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Prostanoid Signaling in Cancers: Expression and Regulation Patterns of Enzymes and Receptors.Biology · 2022Article
- A vicious circle in breast cancer: The interplay between inflammation, reactive oxygen species, and microRNAs.Frontiers in oncology · 2022Review
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProstaglandin is one of the key metabolites for inflammation-related carcinogenesis. Despite the microRNA-155 is implicated in various types of cancers, it's function in prostaglandin metabolism is largely unknown.
methodsA targeted profiling of eicosanoids including prostaglandin, leukotriene and thromboxanes was performed in miR-155 deficient breast tumors and cancer cells. The molecular mechanism of miR-155-mediated prostaglandin reprogramming was investigated in primary and cancer cell lines, by analyzing key enzymes responsible for the prostaglandin production.
resultsWe found miR-155-deficient breast tumors, plasma of tumor-bearing mouse and cancer cells show altered prostaglandin level, especially for the prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2). Subsequent analysis in primary cancer cells, 20 triple-negative breast cancer (TNBC) specimens and breast cancer cell lines with miR-155 knockdown consistently showed a positive correlation between miR-155 level and PGE2/PGD2 ratio. Mechanistically, we reveal the miR-155 reprograms the prostaglandin metabolism by up-regulating PGE2-producing enzymes PTGES/PTGES2 while down-regulating PGD2-producing enzyme PTGDS. Further, we show the up-regulation of PTGES2 is driven by miR-155-cMYC axis, whereas PTGES is transactivated by miR-155-KLF4. Thus, miR-155 hires dual-regulatory mode for the metabolic enzyme expression to reprogram the PGE2/PGD2 balance. Lastly, we show the miR-155-driven cellular proliferation is restored by the siRNA of PTGES1/2, of which expression also significantly correlates with breast cancer patients' survival.
conclusionsConsidering clinical trials targeting PGE2 production largely have focused on the inhibition of Cox1 or Cox2 that showed cardiac toxicity, our data suggest an alternative way for suppressing PGE2 production via the inhibition of miR-155. As the antagomiR of miR-155 (MRG-106) underwent a phase-1 clinical trial, its effect should be considered and analyzed in prostaglandin metabolism in tumor.
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