Exosomes derived from miR-1228 overexpressing bone marrow-mesenchymal stem cells promote growth of gastric cancer cells

Aging (Albany NY). 2021 Apr 21;13(8):11808-11821. doi: 10.18632/aging.202878. Epub 2021 Apr 21.

Abstract

There has been increasing evidence that microRNAs (miRNAs) are related to glioma progression, and that genetically engineered mesenchymal stem cells (MSCs) can inhibit the growth of gliomas. However, the underlying mechanism of bone marrow-MSCs (BM--MSCs) and miRs in gastric cancer still remains unclear. Patients with gastric cancer treated in Shijiazhuang First Hospital as well as healthy individuals undergoing physical examinations were recruited to measure the expression of exosomal miR-1228. Receiver operating characteristic (ROC) curves were plotted and the patients were followed up. BM--MSCs from healthy subjects were collected and exosomes were extracted. The MSC cells were transfected with lentiviral vectors carrying miR-1228 and MMP-14 over-expression sequences and scramble sequence, followed by exosome extraction. The exosomes were co-cultured with SGC-7901 and MGC-823 cells to detect cell proliferation, invasion, apoptosis and migration. The correlation between miR-1228 and MMP-14 was determined by dual-luciferase reporter assay. miR-1228 was highly expressed in serum exosomes of patients with gastric cancer with a area under ROC curve (AUC) of 0.865. The exosomes derived from BM-MSCs are expected to be efficient nanocarriers. Up-regulation of miR-1228 can down-regulate the expression of MMP-14 and effectively hinders the development and progression of gastric cancer.

Keywords: MMP-14; bone marrow-mesenchymal stem cells; exosomes; gastric cancer; miR-1228.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Bone Marrow / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Coculture Techniques
  • Down-Regulation
  • Exosomes / genetics
  • Exosomes / metabolism
  • Female
  • Follow-Up Studies
  • Gastric Mucosa / cytology
  • Gastric Mucosa / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Healthy Volunteers
  • Humans
  • Male
  • Matrix Metalloproteinase 14 / genetics*
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MIRN1228 microRNA, human
  • MicroRNAs
  • MMP14 protein, human
  • Matrix Metalloproteinase 14