Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-181a retards nasopharyngeal carcinoma development by mediating KDM5C

J Cancer Res Clin Oncol. 2021 Oct;147(10):2867-2877. doi: 10.1007/s00432-021-03684-6. Epub 2021 Jul 4.

Abstract

Objective: It has been studied that mesenchymal stem cells (MSCs)-derived exosomes could suppress tumor growth in nasopharyngeal carcinoma (NPC) and microRNA-181a (miR-181a) could mediate drug resistance in NPC. Focused on this work, the mechanism of human umbilical cord MSCs (hUC-MSCs)-derived exosomal miR-181a was explored in NPC cell progression.

Methods: NPC tissues and normal tissues were obtained from patients, and miR-181a and KDM5C expression was examined. hUC-MSCs-derived exosomes were extracted, identified and co-cultured with NPC cells (C666-1 and SUNE1). C666-1 cell progression in vitro and/or tumor growth in vivo were examined after incubation with exosomes, miR-181a or lysine-specific demethylase 5C (KDM5C). miR-181a and KDM5C expression were examined in NPC.

Results: miR-181a expression was reduced while KDM5C expression was elevated in NPC. hUC-MSCs-derived exosomes restrained NPC cell growth in vivo and in vitro. Depleting or restoring exosomal miR-181a promoted or delayed NPC cell progression. KDM5C silencing suppressed NPC cell progression.

Conclusion: This study concluded that hUC-MSCs-derived exosomal miR-181a retards NPC development via negatively modulating KDM5C, serving as a candidate reference for the therapy of NPC.

Keywords: Exosomes; Human umbilical cord mesenchymal stem cells; Lysine specific demethylase 5C; MicroRNA-181a; Nasopharyngeal carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Movement
  • Cell Proliferation
  • Exosomes / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / prevention & control*
  • Prognosis
  • Tumor Cells, Cultured
  • Umbilical Cord / cytology
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MIrn181 microRNA, human
  • MicroRNAs
  • Histone Demethylases
  • KDM5C protein, human