microRNA-155-3p delivered by M2 macrophages-derived exosomes enhances the progression of medulloblastoma through regulation of WDR82

J Transl Med. 2022 Jan 4;20(1):13. doi: 10.1186/s12967-021-03156-y.

Abstract

Objective: Exosomes, 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).

Methods: miR-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.

Results: miR-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.

Conclusion: The 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.

Keywords: Apoptosis; Exosomes; Invasion; M2 macrophages; Medulloblastoma; MicroRNA-155-3p; Migration; Proliferation; WD repeat domain 82.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cerebellar Neoplasms*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Exosomes* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Macrophages / metabolism
  • Medulloblastoma* / genetics
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • MIRN155 microRNA, human
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Wdr82 protein, mouse