miR-130b-3p inhibits cell invasion and migration by targeting the Notch ligand Delta-like 1 in breast carcinoma

Gene. 2017 Apr 20:609:80-87. doi: 10.1016/j.gene.2017.01.036. Epub 2017 Feb 3.

Abstract

Breast carcinoma is the most common malignancy in women, and the incidence rate has increased dramatically in recent years. Metastasis is responsible for most advanced breast cancer mortality, but the underlying mechanisms remain poorly understood despite extensive research. Recently, short non-coding RNA molecules, including miRNAs, which mediate changes in signalling pathways, have emerged as metastatic regulators of the breast carcinoma. Previous reports have suggested that miR-130b-3p has both oncogenic and tumour suppressor functions in a cancer type-dependent manner. However, the roles and underlying molecular mechanisms of miR-130b-3p in the development of metastasis in breast carcinoma remain unclear. Here, we reported for the first time that miR-130b-3p was differentially expressed in early-stage non-invasive MCF-7 human breast carcinoma cells and aggressive late-stage MDA-MB-231 cells. In gain-of-function and loss-of-function studies, we demonstrated that miR-130b-3p could inhibit breast carcinoma cell invasion and migration by directly targeting the Notch ligand Delta-like 1 (DLL1). Our data also indicated that MMP-9, MMP-13, and VEGF were regulated by miR-130b-3p and may be involved in the inhibition of cell invasion and migration in breast carcinoma. Collectively, our findings reveal a new regulatory mechanism of miR-130b-3p and suggest that miR-130b-3p may be a potential target against human breast cancer metastasis.

Keywords: Breast cancer; Dll1; Invasion; Migration; miR-130b-3p; miRNA.

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Calcium-Binding Proteins
  • Cell Line, Tumor
  • Cell Movement*
  • Down-Regulation
  • Gene Expression Regulation, Developmental
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Matrix Metalloproteinases / metabolism
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN130 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinases