Proestler, Eva ; Donzelli, Julia ; Nevermann, Sheila ; Breitwieser, Kai ; Koch, Leon F. ; Best, Tatjana ; Fauth, Maria ; Wickström, Malin ; Harter, Patrick N. ; Kogner, Per ; Lavieu, Grégory ; Larsson, Karin ; Saul, Meike J. (2023)
The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment.
In: Frontiers in Pharmacology, 14
doi: 10.3389/fphar.2023.1183720
Article, Bibliographie
This is the latest version of this item.
Abstract
Neuroblastoma is the most common extracranial solid tumor in childhood and arises from neural crest cells of the developing sympathetic nervous system. Prostaglandin E₂ (PGE₂) has been identified as a key pro-inflammatory mediator of the tumor microenvironment (TME) that promotes neuroblastoma progression. We report that the interaction between the microRNA miR-574-5p and CUG-binding protein 1 (CUGBP1) induces the expression of microsomal prostaglandin E₂ synthase 1 (mPGES-1) in neuroblastoma cells, which contributes to PGE₂ biosynthesis. PGE₂ in turn specifically induces the sorting of miR-574-5p into small extracellular vesicles (sEV) in neuroblastoma cell lines. sEV are one of the major players in intercellular communication in the TME. We found that sEV-derived miR-574-5p has a paracrine function in neuroblastoma. It acts as a direct Toll-like receptor 7/8 (TLR7/8) ligand and induces α-smooth muscle actin (α-SMA) expression in fibroblasts, contributing to fibroblast differentiation. This is particularly noteworthy as it has an opposite function to that in the TME of lung carcinoma, another PGE₂ dependent tumor type. Here, sEV-derived miR-574-5p has an autokrine function that inhibits PGE₂ biosynthesis in lung cancer cells. We report that the tetraspanin composition on the surface of sEV is associated with the function of sEV-derived miR-574-5p. This suggests that the vesicles do not only transport miRs, but also appear to influence their mode of action.
Item Type: | Article |
---|---|
Erschienen: | 2023 |
Creators: | Proestler, Eva ; Donzelli, Julia ; Nevermann, Sheila ; Breitwieser, Kai ; Koch, Leon F. ; Best, Tatjana ; Fauth, Maria ; Wickström, Malin ; Harter, Patrick N. ; Kogner, Per ; Lavieu, Grégory ; Larsson, Karin ; Saul, Meike J. |
Type of entry: | Bibliographie |
Title: | The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment |
Language: | English |
Date: | 2023 |
Place of Publication: | Lausanne |
Publisher: | Frontiers Media S.A. |
Journal or Publication Title: | Frontiers in Pharmacology |
Volume of the journal: | 14 |
Collation: | 17 Seiten |
DOI: | 10.3389/fphar.2023.1183720 |
Corresponding Links: | |
Abstract: | Neuroblastoma is the most common extracranial solid tumor in childhood and arises from neural crest cells of the developing sympathetic nervous system. Prostaglandin E₂ (PGE₂) has been identified as a key pro-inflammatory mediator of the tumor microenvironment (TME) that promotes neuroblastoma progression. We report that the interaction between the microRNA miR-574-5p and CUG-binding protein 1 (CUGBP1) induces the expression of microsomal prostaglandin E₂ synthase 1 (mPGES-1) in neuroblastoma cells, which contributes to PGE₂ biosynthesis. PGE₂ in turn specifically induces the sorting of miR-574-5p into small extracellular vesicles (sEV) in neuroblastoma cell lines. sEV are one of the major players in intercellular communication in the TME. We found that sEV-derived miR-574-5p has a paracrine function in neuroblastoma. It acts as a direct Toll-like receptor 7/8 (TLR7/8) ligand and induces α-smooth muscle actin (α-SMA) expression in fibroblasts, contributing to fibroblast differentiation. This is particularly noteworthy as it has an opposite function to that in the TME of lung carcinoma, another PGE₂ dependent tumor type. Here, sEV-derived miR-574-5p has an autokrine function that inhibits PGE₂ biosynthesis in lung cancer cells. We report that the tetraspanin composition on the surface of sEV is associated with the function of sEV-derived miR-574-5p. This suggests that the vesicles do not only transport miRs, but also appear to influence their mode of action. |
Uncontrolled Keywords: | miR-574-5p, TLR7/8, PGE₂, tetraspanins, neuroblastoma, NSCLC |
Additional Information: | Sec. Inflammation Pharmacology |
Classification DDC: | 500 Science and mathematics > 570 Life sciences, biology 600 Technology, medicine, applied sciences > 610 Medicine and health |
Divisions: | 10 Department of Biology 10 Department of Biology > Extracellular vesicles / miRNA Research |
Date Deposited: | 22 Jan 2024 09:05 |
Last Modified: | 22 Jan 2024 09:05 |
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The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment. (deposited 19 Jan 2024 14:02)
- The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment. (deposited 22 Jan 2024 09:05) [Currently Displayed]
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