miR-124-3p functions as a tumor suppressor in breast cancer by targeting CBL

BMC Cancer. 2016 Nov 15;16(1):826. doi: 10.1186/s12885-016-2862-4.

Abstract

Background: The origin and development of breast cancer remain complex and obscure. Recently, microRNA (miRNA) has been identified as an important regulator of the initiation and progression of breast cancer, and some studies have shown the essential role of miR-124-3p as a tumor suppressor in breast tumorigenesis. However, the detailed role of miR-124-3p in breast cancer remains poorly understood.

Methods: Quantitative RT-PCR and western blotting assays were used to measure miR-124-3p and CBL expression levels in breast cancer tissues, respectively. Luciferase reporter assay was employed to validate the direct targeting of CBL by miR-124-3p. Cell proliferation and invasion assays were performed to analyze the biological functions of miR-124-3p and CBL in breast cancer cells.

Results: In the present study, we found that miR-124-3p was consistently downregulated in breast cancer tissues. Moreover, we showed that miR-124-3p significantly suppressed the proliferation and invasion of breast cancer cells. In addition, we investigated the molecular mechanism through which miR-124-3p contributes to breast cancer tumorigenesis and identified CBL (Cbl proto-oncogene, E3 ubiquitin protein ligase) as a direct target gene of miR-124-3p. Moreover, we found that ectopic expression of CBL can attenuate the inhibitory effect of miR-124-3p on cell proliferation and invasion in breast cancer cells.

Conclusions: This study identified a new regulatory axis in which miR-124-3p and CBL regulate the proliferation and invasion of breast cancer cells.

Keywords: Breast cancer; CBL; Invasion; Proliferation; miR-124-3p.

MeSH terms

  • 3' Untranslated Regions
  • Base Pairing
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Genes, Tumor Suppressor*
  • Humans
  • MicroRNAs / genetics*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-cbl / genetics*
  • RNA Interference*
  • Reproducibility of Results

Substances

  • 3' Untranslated Regions
  • MAS1 protein, human
  • MIRN124 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-cbl
  • CBL protein, human