Bone marrow mesenchymal stem cells-derived exosomal microRNA-193a reduces cisplatin resistance of non-small cell lung cancer cells via targeting LRRC1

Cell Death Dis. 2020 Sep 25;11(9):801. doi: 10.1038/s41419-020-02962-4.

Abstract

Exosomes are small endogenous membrane vesicles that can mediate cell communication by transferring genetic materials. Based on that, exosomes have always been discussed as a cargo carrier for microRNA (miRNA) transportation. Accumulating data have reported the inhibitory effects of microRNA-193a (miR-193a) on non-small cell lung cancer (NSCLC) cell progression. However, the mechanisms of miR-193a delivery to cancer cells and miR-193a in exosomes have not been explored clearly in NSCLC. Given that, this work aims to decode exosomal miR-193a in cisplatin (DDP) resistance of NSCLC cells. A549 and H1299 cell lines were screened out and their parent cells and drug-resistant cells were co-cultured with human bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exo) that had been transfected with miR-193a mimic or si-LRRC1 to detect the colony formation, migration, apoptosis, invasion and proliferation of NSCLC cells. In vivo experiment was conducted to verify the in vitro results. BMSC-Exo with upregulated miR-193a and downregulated LRRC1 suppressed colony formation, invasion, proliferation and migration as well as advanced apoptosis of NSCLC parent cells and drug-resistant cells. BMSC-Exo combined with upregulated miR-193a reduced tumor volume and weight in mice with NSCLC. Functional studies report that BMSC-Exo shuffle miR-193a to suppress the colony formation, invasion, migration, and proliferation as well as advance apoptosis of NSCLC DDP-resistant cells via downregulating LRRC1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carrier Proteins / metabolism*
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm / drug effects*
  • Exosomes / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Membrane Proteins / metabolism*
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs
  • Middle Aged
  • Transfection

Substances

  • Carrier Proteins
  • LRRC1 protein, human
  • MIRN193 microRNA, mouse
  • Membrane Proteins
  • MicroRNAs
  • Cisplatin