MicroRNA-137 Inhibits Cancer Progression by Targeting Del-1 in Triple-Negative Breast Cancer Cells

Int J Mol Sci. 2019 Dec 6;20(24):6162. doi: 10.3390/ijms20246162.

Abstract

MicroRNAs (miRNAs) can be used to target a variety of human malignancy by targeting their oncogenes or tumor suppressor genes. The developmental endothelial locus-1 (Del-1) might be under miRNA regulation. This study investigated microRNA-137 (miR-137) function and Del-1 expression in triple-negative breast cancer (TNBC) cells and tissues. Del-1 mRNA and miRNA-137 levels were determined via qRT-PCR in breast cancer cells (MDA-MB-231, MCF7, SK-BR3, and T-47D) and tissues from 30 patients with TNBC. The effects of miR-137 on cell proliferation, migration, and invasion were determined using MTT assays, wound healing, and Matrigel transwell assays. The luciferase reporter assay revealed direct binding of miR-137 to the 3'-UTR of Del-1. miR-137 inhibited cell proliferation, migration, and invasion of MDA-MB-231 cells. Among the 30 TNBC specimens, miR-137 was downregulated and Del-1 level in plasma was significantly elevated relative to normal controls. It is concluded that miR-137 regulates Del-1 expression in TNBC by directly binding to the Del-1 gene and cancer progression. The results implicate miR-137 as a new therapeutic biomarker for patients with TNBC.

Keywords: Del-1; biomarker; developmental endothelial locus-1; miR-137; triple-negative breast cancer.

MeSH terms

  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Plasmids / genetics
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism*

Substances

  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • EDIL3 protein, human
  • MIRN137 microRNA, human
  • MicroRNAs