miR-135b promotes proliferation and metastasis by targeting APC in triple-negative breast cancer

J Cell Physiol. 2019 Jul;234(7):10819-10826. doi: 10.1002/jcp.27906. Epub 2019 Jan 9.

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. The aim of our study was to investigate the functional role of microRNA-135b (miR-135b) in TNBC. A real-time polymerase chain reaction assay was used to quantify miR-135b expression levels in 90 paired TNBC tissue and adjacent normal tissue samples. Wound-healing and transwell assays were performed to evaluate the effects of miR-135b expression on the migration and invasion of TNBC cells. Luciferase reporter and western blot analyses were used to verify whether the mRNA encoding APC is a major target of miR-135b. In the current study, we found that miR-135b was highly expressed in TNBC tissue and cells, and the expression levels were correlated with lymph node status and TNM stage. In TNBC cells, the ectopic expression of miR-135b promoted cell proliferation and invasion in vitro. In addition, our study proved that the overexpression of miR-135b significantly suppressed APC expression by targeting the 3'-untranslated region of APC, whereas enhanced APC expression could partially abrogate the miR-135b-mediated promotion of carcinogenic traits in TNBC cells. Taken together, our study demonstrated that miR-135b expression promoted the proliferation and invasion of TNBC by downregulating APC expression, indicating that miR-135b may serve as a promising target for the treatment of TNBC patients.

Keywords: APC; invasion; miR-135b; proliferation; triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Adult
  • Cell Movement*
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Signal Transduction
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • MIRN135 microRNA, human
  • MicroRNAs