MiR-34a Inhibits Breast Cancer Proliferation and Progression by Targeting Wnt1 in Wnt/β-Catenin Signaling Pathway

Am J Med Sci. 2016 Aug;352(2):191-9. doi: 10.1016/j.amjms.2016.05.002. Epub 2016 May 7.

Abstract

Background: As microRNA-34a (miR-34a) has been suggested to be associated with breast cancer (BC), this study was proposed to explore the underlying mechanism of miR-34a in suppressing BC progression.

Methods: A total of 123 pairs of tumor tissues and matched nontumor tissues were obtained from patients. Reverse transcription polymerase chain reaction and in situ hybridization were used to detect the differences in miR-34a expression in tissues and cells. Whether Wnt1 is a direct downstream target of miR-34a was confirmed by both bioinformatics target gene prediction and dual-luciferase report assay. Wnt1 and other gene expressions that are related to Wnt/β-catenin signaling pathway were assessed by reverse transcription polymerase chain reaction and western blot when MCF-7A cells were transfected with miR-34a mimic or miR-34a inhibitor. The proliferation, invasion and migration status of MCF-7 cells after transfection were assessed by MTT assay, wound healing assay and transwell assays, respectively. Breast tumor xenograft models on mice were also constructed to determine the effect of miR-34a on breast tumor growth in vivo.

Results: MiR-34a expression was remarkably down-regulated in BC tissues and cell lines compared with normal tissues and cell lines. Wnt1 was a direct downstream target of miR-34a and low expression of miR-34a contributed to the Wnt/β-catenin signaling pathway activation in MCF-7A cells. MiR-34a inhibited the proliferation, invasion and migration of BC in vitro and breast tumor growth in vivo through deactivating the Wnt/β-catenin signaling pathway.

Conclusion: MiR-34a may suppress the proliferation and progression of BC via mediating the Wnt/β-catenin signaling pathway.

Keywords: Breast cancer; Wnt/β-catenin signaling pathway; Wnt1; Xenograft model; microRNA-34a.

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Cell Proliferation / physiology*
  • Disease Progression*
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • Wnt Signaling Pathway / physiology*
  • Wnt1 Protein / antagonists & inhibitors
  • Wnt1 Protein / metabolism*
  • Xenograft Model Antitumor Assays / methods

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • WNT1 protein, human
  • Wnt1 Protein