Abstract
ObjectiveExosomes, membranous nanovesicles, naturally bringing proteins, mRNAs, and microRNAs (miRNAs), play crucial roles in tumor pathogenesis. This study was to investigate the role of miR-155-3p from M2 macrophages-derived exosomes (M2-Exo) in promoting medulloblastoma (MB) progression by mediating WD repeat domain 82 (WDR82).MethodsmiR-155-3p expression was detected by RT-qPCR. The relationship of miR-155-3p with clinicopathological features of MB patients was analyzed. M2-Exo were isolated and identified by TEM, NTA and Western blot. CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were performed to explore the role of miR-155-3p-enriched M2-Exo on the progression of MB cells. Luciferase assay were used to identify the relationship between miR-155-3p and WDR82. The effect of miR-155-3p-enriched M2-Exo on tumorigenesis of MB was confirmed by the xenograft nude mice model.ResultsmiR-155-3p was up-regulated in MB tissues of patients and MB cell lines. High miR-155-3p expression was correlated with the pathological type and molecular subtype classification of MB patients. WDR82 was a direct target of miR-155-3p. miR-155-3p was packaged into M2-Exo. miR-155-3p-enriched M2-Exo promoted the progression of Daoy cells. miR-155-3p-enriched M2-Exo promoted in vivo tumorigenesis.ConclusionThe study highlights that miR-155-3p-loaded M2-Exo enhances the growth of MB cells via down-regulating WDR82, which might provide a deep insight into MB mechanism.
Highlights
Medulloblastoma (MB) is a most prevalent malignancy in children [1]
An important form of extracellular vesicles, have been confirmed as the intercellular communication mediators in various physical processes related to cell proliferation and migration [13]
We first characterized the exosomes to determine their size, appearance and expression of protein exosomal markers, in accordance with recommendations by minimal information for studies of extracellular vesicles 2018 (MISEV2018) [17], and explored that whether M2 macrophages-derived exosomes (M2-Exo) could load miR-155-3p to mediate the progression of MB cells
Summary
Medulloblastoma (MB) is a most prevalent malignancy in children [1]. The occurrence of MB is the highest in brain tumors, while its prognosis is much unpleasing [2, 3]. Macrophages are inborn immune cells that could modify different kinds of immune responses, antigen presentation and phagocytosis. After differentiation from their monocyte precursor, macrophages polarize toward M1-like or M2-like phenotype [12]. An important form of extracellular vesicles, have been confirmed as the intercellular communication mediators in various physical processes related to cell proliferation and migration [13]. We first characterized the exosomes to determine their size, appearance and expression of protein exosomal markers, in accordance with recommendations by minimal information for studies of extracellular vesicles 2018 (MISEV2018) [17], and explored that whether M2 macrophages-derived exosomes (M2-Exo) could load miR-155-3p to mediate the progression of MB cells. It has been accepted that WDR82 reduction is correlated with a poor prognosis of patients with colorectal cancer (CRC) [21], while the relationship of WDR82 with MB was little studied
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