ArticleCell research2015
Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment.
Article in Cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed.
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- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The role of lipid metabolic interactions in reshaping the tumor microenvironment.Acta biochimica et biophysica Sinica · 2025Article
- CAFs exosomal circFOXO1 promotes TNBC autophagy and radioresistance via miR-27a-3p/BNIP3 axis.Scientific reports · 2025Article
- Integrating single-cell and spatial transcriptomics reveals the cellular heterogeneity of vestibular schwannoma.NPJ precision oncology · 2025Article
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- Targeting KRAS: from metabolic regulation to cancer treatment.Molecular cancer · 2025Review
- Development and preliminary validation of five miRNAs for lung adenocarcinoma prognostic model associated with immune infiltration.Scientific reports · 2025Article
- Single-cell RNA-Seq reveals the heterogeneity of fibroblasts within the tympanojugular paraganglioma microenvironment.Heliyon · 2024Article
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- Decoding the Tumour Microenvironment: Molecular Players, Pathways, and Therapeutic Targets in Cancer Treatment.Cancers · 2024Review
- Urinary miRNAs: Technical Updates.MicroRNA (Shariqah, United Arab Emirates) · 2024Review
- Epigenetic modulation of cytokine expression in gastric cancer: influence on angiogenesis, metastasis and chemoresistance.Frontiers in immunology · 2024Review
- Cancer metastasis under the magnifying glass of epigenetics and epitranscriptomics.Cancer metastasis reviews · 2023Review
- Cancer-Associated Fibroblasts in Gastrointestinal Cancers: Unveiling Their Dynamic Roles in the Tumor Microenvironment.International journal of molecular sciences · 2023Review
- Exo-miR-1290-induced by COX-2 overexpression promotes cancer-associated fibroblasts activation and tumor progression by CUL3-Nrf2 pathway in lung adenocarcinoma.Cell communication and signaling : CCS · 2023Article
- MicroRNA based combinatorial therapy against TKIs resistant CML by inactivating the PI3K/Akt/mTOR pathway: a review.Medical oncology (Northwood, London, England) · 2023Review
- Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection.BMC medical genomics · 2023Article
- Epigenetic regulation of cancer-associated fibroblast heterogeneity.Biochimica et biophysica acta. Reviews on cancer · 2023Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors.
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Abstract
Tumor initiation and growth depend on its microenvironment in which cancer-associated fibroblasts (CAFs) in tumor stroma play an important role. Prostaglandin E2 (PGE2) and interleukin (IL)-6 signal pathways are involved in the crosstalk between tumor and stromal cells. However, how PGE2-mediated signaling modulates this crosstalk remains unclear. Here, we show that microRNA (miR)-149 links PGE2 and IL-6 signaling in mediating the crosstalk between tumor cells and CAFs in gastric cancer (GC). miR-149 inhibited fibroblast activation by targeting IL-6 and miR-149 expression was substantially suppressed in the CAFs of GC. miR-149 negatively regulated CAFs and their effect on GC development both in vitro and in vivo. CAFs enhanced epithelial-to-mesenchymal transition (EMT) and the stem-like properties of GC cells in a miR-149-IL-6-dependent manner. In addition to IL-6, PGE2 receptor 2 (PTGER2/EP2) was revealed as another potential target of miR-149 in fibroblasts. Furthermore, H. pylori infection, a leading cause of human GC, was able to induce cyclooxygenase-2 (COX-2)/PGE2 signaling and to enhance PGE2 production, resulting in the hypermethylation of miR-149 in CAFs and increased IL-6 secretion. Our findings indicate that miR-149 mediates the crosstalk between tumor cells and CAFs in GC and highlight the potential of interfering miRNAs in stromal cells to improve cancer therapy.
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