MicroRNA-188-5p promotes apoptosis and inhibits cell proliferation of breast cancer cells via the MAPK signaling pathway by targeting Rap2c

J Cell Physiol. 2020 Mar;235(3):2389-2402. doi: 10.1002/jcp.29144. Epub 2019 Sep 20.

Abstract

Breast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically involved in different cancer remedies, but their mechanism in breast cancer has not been elucidated for prospective treatment. The function and mechanism of microRNA-188-5p (miR-188) have not been thoroughly investigated in breast cancer. In our study, we found that the expression of miR-188 in breast cancer tissues was obviously reduced. Our findings also revealed the abnormal overexpression of miR-188 in 4T1 and MCF-7 cells significantly suppressed cell proliferation and migration and also enhanced apoptosis. miR-188 induced cell cycle arrest in the G1 phase. To illuminate the molecular mechanism of miR-188, Rap2c was screened as a single target gene by bioinformatics database analysis and was further confirmed by dual-luciferase assay. Moreover, Rap2c was found to be a vital molecular switch for the mitogen-activated protein kinase signaling pathway in tumor progression by decreasing apoptosis and promoting proliferation and migration. In conclusion, our results revealed that miR-188 is a cancer progression suppressor and a promising future target for breast cancer therapy.

Keywords: MAPK; Rap2c; apoptosis; breast cancer; miR-188-5p; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MAP Kinase Signaling System / genetics
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • ras Proteins / genetics*

Substances

  • MIRN188 microRNA, human
  • MicroRNAs
  • Rap2C protein, human
  • ras Proteins