Tumor-derived exosomal miR-3157-3p promotes angiogenesis, vascular permeability and metastasis by targeting TIMP/KLF2 in non-small cell lung cancer

Cell Death Dis. 2021 Sep 8;12(9):840. doi: 10.1038/s41419-021-04037-4.

Abstract

Metastasis is the main cause of death in patients with advanced lung cancer. The exosomes released by cancer cells create tumor microenvironment, and then accelerate tumor metastasis. Cancer-derived exosomes are considered to be the main driving force for metastasis niche formation at foreign sites, but the mechanism in Non-small cell lung carcinoma (NSCLC) is unclear. In metastatic NSCLC patients, the expression level of miR-3157-3p in circulating exosomes was significantly higher than that of non-metastatic NSCLC patients. Here, we found that miR-3157-3p can be transferred from NSCLC cells to vascular endothelial cells through exosomes. Our work indicates that exosome miR-3157-3p is involved in the formation of pre-metastatic niche formation before tumor metastasis and may be used as a blood-based biomarker for NSCLC metastasis. Exosome miR-3157-3p has regulated the expression of VEGF/MMP2/MMP9 and occludin in endothelial cells by targeting TIMP/KLF2, thereby promoted angiogenesis and increased vascular permeability. In addition, exosome miR-3157-3p promoted the metastasis of NSCLC in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor / metabolism
  • Capillary Permeability / genetics*
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Exosomes / metabolism*
  • Exosomes / ultrastructure
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Kruppel-Like Transcription Factors / metabolism*
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / genetics*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / genetics*
  • ROC Curve
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*
  • Up-Regulation / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN3157 microRNA, human
  • MicroRNAs
  • Tissue Inhibitor of Metalloproteinase-2