MiR-577 suppresses epithelial-mesenchymal transition and metastasis of breast cancer by targeting Rab25

Thorac Cancer. 2018 Apr;9(4):472-479. doi: 10.1111/1759-7714.12612. Epub 2018 Mar 10.

Abstract

Background: MicroRNAs can act as both tumor suppressor genes and oncogenes and participate in cell proliferation, metastasis, and apoptosis. Low levels of miR-577 are found in several cancers, for example, thyroid carcinoma, glioblastoma, and hepatocellular carcinoma. The aim of this study was to investigate the effect of miR-577 on breast cancer (BC).

Methods: The relative level of miR-577 in 120 BC tissues and cells was detected by real-time PCR. MDA-MB-231 cells with upregulated miR-577 and MCF-7 cells with downregulated miR-577 were established. Transwell invasion assays were used to examine the invasiveness of cells. Epithelial-mesenchymal transition (EMT) markers were evaluated by immunofluorescence and Western blot. Targeted combinations of miR-577 and Rab25 were analyzed by luciferase assays. Xenograft models were used to examine the effect of miR-577 on BC metastasis.

Results: MiR-577 expression was significantly suppressed in BC tissues. Tumor size, tumor stage, and lymphatic metastasis were attributed to miR-577 expression. Moreover, miR-577 overexpression strongly inhibited the invasiveness and EMT of BC cells in vitro. MiR-577 directly regulated Rab25 in BC. Rab25 upregulation by miR-577 decreased the levels of E-cadherin and increased the levels of Vimentin. Notably, Rab25 knockdown inhibited BC invasion; however, an increase in Rab25 counteracted the invasive effect of miR-577 in BC.

Conclusion: Results indicated that miR-577 suppressed EMT by inhibiting Rab25 expression in BC. MiR-577 and Rab25 are considered potential targets of BC treatment.

Keywords: Breast cancer; MiR-577; Rab25; epithelial-mesenchymal transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lymphatic Metastasis
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • rab GTP-Binding Proteins / genetics*

Substances

  • MIRN577 microRNA, human
  • MicroRNAs
  • Rab25 protein, human
  • rab GTP-Binding Proteins