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. (2024)
The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment.
In: Frontiers in Pharmacology, 2023, 14
doi: 10.26083/tuprints-00024551
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | 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. |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment |
| Sprache: | Englisch |
| Publikationsjahr: | 19 Januar 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2023 |
| Ort der Erstveröffentlichung: | Lausanne |
| Verlag: | Frontiers Media S.A. |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Frontiers in Pharmacology |
| Jahrgang/Volume einer Zeitschrift: | 14 |
| Kollation: | 17 Seiten |
| DOI: | 10.26083/tuprints-00024551 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/24551 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (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. |
| Freie Schlagworte: | miR-574-5p, TLR7/8, PGE₂, tetraspanins, neuroblastoma, NSCLC |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-245517 |
| Zusätzliche Informationen: | Sec. Inflammation Pharmacology |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Extracellular vesicles / miRNA Research |
| Hinterlegungsdatum: | 19 Jan 2024 14:02 |
| Letzte Änderung: | 22 Jan 2024 09:04 |
| PPN: | |
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| Suche nach Titel in: | TUfind oder in Google |
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- The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment. (deposited 19 Jan 2024 14:02) [Gegenwärtig angezeigt]
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