Inhibition effect of exosomes-mediated Let-7a on the development and metastasis of triple negative breast cancer by down-regulating the expression of c-Myc

Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5301-5314. doi: 10.26355/eurrev_201906_18197.

Abstract

Objective: Triple negative breast cancer is typically characterized by high malignancy, easy recurrence and metastasis, and poor prognosis. However, effective treatment for triple negative breast cancer has not yet been identified. Our research explores the underlying mechanisms of exosomes in transporting Let-7a and regulating c-Myc gene and their roles in the development of triple negative breast cancer, and to provide new ideas for targeted therapy of triple negative breast cancer.

Patients and methods: Based on previous studies that focused on the roles of c-Myc and Let-7a in the development of triple negative breast cancer, triple negative breast cancer cell lines have been constructed by c-Myc knockout and overexpression of Let-7a, respectively, to evaluate the effects of c-Myc, and Let-7a, as well as exosomes transmitting Let-7a on the development of triple negative breast cancer.

Results: Let-7a, which is mediated by exosomes, inhibited proliferation, migration, and invasion of MDA-MB-231 cells by binding on the 3'UTR region of the c-Myc gene and silencing of the c-Myc expression.

Conclusions: Our study revealed the role of c-Myc, Let-7a, and exosomes in the development of triple negative breast cancer, which lay the theoretical foundation for further usage of exosomes to construct tumor killing vectors and for exploring specific targets for triple negative breast cancer.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Biopsy
  • Breast / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Exosomes / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Survival Analysis
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • mirnlet7 microRNA, human