Mesenchymal stem cells-derived exosomal miR-653-5p suppresses laryngeal papilloma progression by inhibiting BZW2

Clinics (Sao Paulo). 2022 Dec 3:78:100129. doi: 10.1016/j.clinsp.2022.100129. eCollection 2023.

Abstract

Objectives: Although miR-653-5p has been validated to participate in the progression of multiple types of cancer, the functional role of exosomal miR-653-5p derived from Mesenchymal Stem Cells (MSCs) in Laryngeal Papilloma (LP) has still remained elusive. Hence, this study aimed to investigate the role of MSCs-derived exosomal miR-653-5p in LP.

Methods: LP tissues (n = 15) and adjacent normal tissues (n = 10) were collected to examine the expression level of miR-653-5p. The expression level of miR-653-5p in LP cells and normal cells was also detected. Then, miR-653-5p was overexpressed or silenced to explore its effects on the proliferation, migration, invasion, and apoptosis of LP cells. Thereafter, the effects of exosomal miR-653-5p derived from MSCs on LP cell progression and the potential regulatory mechanism of miR-653-5p were assessed.

Results: It was revealed that the expression level of miR-653-5p was downregulated in LP tissues and cells. In addition, miR-653-5p suppressed the proliferation, migration, invasion, and apoptosis of LP cells. Exosomes derived from MSCs played a suppressive role in LP development and mediated the transmission of miR-653-5p to LP cells. Further exploration identified Basic leucine Zipper and W2 domains 2 (BZW2) as the target of miR-653-5p. More importantly, the rescue experiments revealed that MSCs-secreted exosomal miR-653-5p efficiently inhibited the aggressive phenotypes of LP cells, which could be significantly reversed by BZW2 overexpression in LP cells.

Conclusion: MSCs-derived exosomal miR-653-5p exerted inhibitory effects on LP progression through targeting BZW2, which provided a novel idea for the therapy of LP.

Clinical trial registration number: chictr-ior-17011021.

Keywords: Exosomes; Laryngeal Diseases; Mesenchymal Stem Cells; MicroRNAs; Papillomatosis.

MeSH terms

  • Cell Proliferation / genetics
  • DNA-Binding Proteins
  • Humans
  • Laryngeal Neoplasms*
  • Mesenchymal Stem Cells*
  • MicroRNAs* / genetics
  • Papilloma* / metabolism

Substances

  • MicroRNAs
  • BZW2 protein, human
  • DNA-Binding Proteins

Supplementary concepts

  • Laryngeal papillomatosis