Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes

Int J Oncol. 2018 Dec;53(6):2705-2714. doi: 10.3892/ijo.2018.4571. Epub 2018 Sep 25.


Breast cancer is one of the main types of cancer affecting the health of females worldwide. Despite improvements in therapeutic approaches, cancer patients succumb to the disease due to metastasis itself, rather than the primary tumor from which metastases arise, emphasizing the need for the better understanding of the biological bases that contribute to disease progression. RAB22A, a member of the proto-oncogene RAS family, plays an important role in the formation, trafficking and metabolism of exosomes, and is associated with the occurrence and development of multiple human cancers. In this study, we demonstrate that the upregulation of RAB22A is associated with breast cancer progression and lymph node metastasis. We identified a signature of RAB22A and miR-193b that exhibited a negative association in metastatic as opposed to the surrounding normal cells, and RAB22A was identified as the target gene of miR-193b. While RAB22A was found to regulate exosomes-mediated breast cancer cell proliferation, invasion and migration, these biological characteristics were diminished in the breast cancer cells in which the RAB22A gene was knocked down or in the cells in which the exosomes were dissolved by proteinase K/RNase treatment. On the whole, the findings of this study demonstrate the critical role that miR-193b plays in the regulation of RAB22A-mediated exosome function during cancer growth and metastasis, which may have significant implications on cancer therapy.

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Coculture Techniques
  • Exosomes / genetics*
  • Exosomes / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Proto-Oncogene Mas
  • rab GTP-Binding Proteins / genetics*
  • rab GTP-Binding Proteins / metabolism*


  • 3' Untranslated Regions
  • MAS1 protein, human
  • MIRN193 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • RAB22A protein, human
  • rab GTP-Binding Proteins