MicroRNA-224 Promotes Tumorigenesis through Downregulation of Caspase-9 in Triple-Negative Breast Cancer

Dis Markers. 2019 Feb 11;2019:7378967. doi: 10.1155/2019/7378967. eCollection 2019.

Abstract

Triple-negative breast cancer (TNBC) harbors genetic heterogeneity and generally has more aggressive clinical outcomes. As such, there is urgency in identifying new prognostic targets and developing novel therapeutic strategies. In this study, miR-224 was overexpressed in breast cancer cell lines and TNBC primary cancer samples. Knockdown of miR-224 in MDA-MB-231 cancer cells reduced cell proliferation, migration, and invasion. Through integrating in silico prediction algorithms with KEGG pathway and Gene Ontology analyses, CASP9 was identified to be a potential target of miR-224. miR-224 knockdown significantly increased CASP9 transcript and protein levels. Furthermore, luciferase reporter assays confirmed a direct interaction of miR-224 with CASP9. Our findings have demonstrated that the miR-224/CASP9 axis plays an important role in TNBC progression, providing evidence in support of a promising therapeutic strategy for this disease.

MeSH terms

  • Carcinogenesis / genetics*
  • Caspase 9 / genetics*
  • Caspase 9 / metabolism
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • MIRN224 microRNA, human
  • MicroRNAs
  • CASP9 protein, human
  • Caspase 9