MiR-519d suppresses breast cancer tumorigenesis and metastasis via targeting MMP3

Int J Biol Sci. 2018 Feb 9;14(2):228-236. doi: 10.7150/ijbs.22849. eCollection 2018.

Abstract

Breast cancer (BC) is the most common cause of death in women throughout the world. Although microRNAs (miRNAs) have been identified as novel regulators in carcinogenesis, there are still abundant hidden treasure needed to be excavated. In the present study, we found that miR-519d expression was remarkably decreased in both human BC tissues and MCF-7 cells. CCK8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound-healing and transwell assays were performed for detection of cell migration and invasion. The results demonstrated miR-519d overexpression dramatically suppressed MCF-7 cells proliferation, migration and invasion. While downregulation of miR-519d by miR-519d inhibitor substantially increased MCF-7 cell carcinogenesis. Further analysis identified Matrix Metalloproteinase-3 (MMP3) as a direct target of miR-519d. QRT-PCR and western blot results indicated the correlative expression of miR-519d and MMP3 in BC tissues and MCF-7 cells. In summary, our data uncovered the novel molecular interaction between miR-519d and MMP3, indicating a therapeutic strategy of miR-519d for BC.

Keywords: MMP3; breast cancer; metastasis; miR-519d.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics

Substances

  • MIRN519 microRNA, human
  • MicroRNAs
  • Matrix Metalloproteinase 3