miR-186 inhibits proliferation, migration, and epithelial-mesenchymal transition in breast cancer cells by targeting Twist1

J Cell Biochem. 2019 Jun;120(6):10001-10009. doi: 10.1002/jcb.28283. Epub 2018 Dec 14.

Abstract

Objective: Breast cancer (BC) is the most prevalent malignancy in women worldwide. Our study aimed to investigate the expression and biological effect of miR-186 in BC.

Methods: Expression of miR-186 was determined by quantitative reverse transcription PCR. Kaplan-Meier curves were calculated for the survival data analysis. Functional assays were performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound healing assay. Protein expression was analyzed by Western blot.

Results: miR-186 was downregulated in BC tissues and cells. Downregulation of miR-186 was associated with tumor metastasis and a poor overall survival in patients with BC. Overexpression of miR-186 inhibited BC cells proliferation, migration, and epithelial-mesenchymal transition process; while suppression of miR-186 exhibited an opposite effects on BC cells. In addition, Twist1 was identified as a direct target of miR-186 in BC and restoration of Twist1 attenuated the biological effect of miR-186 on BC cells.

Conclusion: Our findings suggest that miR-186 functions as a tumor suppressor by targeting Twist1 in BC. miR-186 may serve as a novel biomarker in BC diagnosis or a new therapeutic target in BC treatment.

Keywords: Twist1; breast cancer (BC); epithelial-mesenchymal transition (EMT); miR-186.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Movement*
  • Cell Proliferation*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Genes, Tumor Suppressor*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Twist-Related Protein 1 / biosynthesis*
  • Twist-Related Protein 1 / genetics

Substances

  • MIRN186 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • Nuclear Proteins
  • RNA, Neoplasm
  • TWIST1 protein, human
  • Twist-Related Protein 1