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The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment

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
Artikel, Bibliographie

Dies ist die neueste Version dieses Eintrags.

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: 2023
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: Bibliographie
Titel: The multiple functions of miR-574-5p in the neuroblastoma tumor microenvironment
Sprache: Englisch
Publikationsjahr: 2023
Ort: Lausanne
Verlag: Frontiers Media S.A.
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Frontiers in Pharmacology
Jahrgang/Volume einer Zeitschrift: 14
Kollation: 17 Seiten
DOI: 10.3389/fphar.2023.1183720
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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.

Freie Schlagworte: miR-574-5p, TLR7/8, PGE₂, tetraspanins, neuroblastoma, NSCLC
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: 22 Jan 2024 09:05
Letzte Änderung: 22 Jan 2024 09:05
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