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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
Article, Bibliographie

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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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