Exosomes from adipose-derived stem cells inhibits skin cancer progression via miR-199a-5p/SOX4

Biotechnol Genet Eng Rev. 2024 Dec;40(4):3950-3962. doi: 10.1080/02648725.2023.2204702. Epub 2023 Apr 24.

Abstract

Although miR-199a-5p is linked to the development of numerous cancers, its regulatory role in skin cancer is unclear. In this work, the impact of miR-199a-5p produced by adipose-derived stem cells on malignant melanoma skin cancer was investigated.30 pair tumor tissues and adjacent tissues were obtained from skin cancer patients. Adipose-derived stem cell (ADSCs) were isolated from adipose tissues harvested from healthy subjects. The mRNA relative expression was evaluated via qRT-PCR. Cell proliferation ability was measured via CCK-8 assay. Apoptosis was evaluated via flow cytometry. The connection between miR-199a-5p and SOX4 was confirmed via luciferase reporter assay. Western blot was conducted to evaluate protein expression. MiR-199a-5p was higher expressed in ADSCs exosomes and was lower expressed in skin cancer tissues and cells. ADSCs-derived exosomes inhibited cell invasion of skin cancer. MiR-199a-5p inhibitor enhanced cell viability and invasion. In addition, miR-199a-5p inhibitor suppressed cell apoptosis. MiR-199a-5p NC transfected ADSCs inhibited cell viability and invasion while miR-199a-5p mimic transfected ADSCs further inhibited cell viability and invasion. In addition, miR-199a-5p NC transfected ADSCs enhanced cell apoptosis while miR-199a-5p mimic transfected ADSCs further enhanced cell apoptosis. Luciferase supported the targetscan prediction that miR-199a-5p might control SOX4 expression. SOX4 expression was noticeably lower in the miR-199a-5p mimic group.Exosomes from adipose-derived stem cells inhibited skin cancer progression via miR-199a-5p/SOX4.

Keywords: Adipose-derived stem cells; MiR-199a-5p; SOX4; melanoma.

MeSH terms

  • Adipose Tissue* / cytology
  • Adipose Tissue* / metabolism
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Exosomes* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • SOXC Transcription Factors* / genetics
  • SOXC Transcription Factors* / metabolism
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • MicroRNAs
  • SOX4 protein, human
  • SOXC Transcription Factors
  • mirn199 microRNA, human