miR-381-3p suppresses breast cancer progression by inhibition of epithelial-mesenchymal transition

World J Surg Oncol. 2021 Aug 6;19(1):230. doi: 10.1186/s12957-021-02344-w.

Abstract

Background: Accumulating evidence indicates that miRNAs are involved in multiple cellular functions and participate in various cancer development and progression, including breast cancer.

Methods: We aimed to investigate the role of miR-381-3p in breast cancer. The expression level of miR-381-3p and EMT transcription factors was examined by quantitative real-time PCR (qRT-PCR). The effects of miR-381-3p on breast cancer proliferation and invasion were determined by Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. The regulation of miR-381-3p on its targets was determined by dual-luciferase analysis, qRT-PCR, and western blot.

Results: We found that the expression of miR-381-3p was significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-381-3p inhibited breast cancer proliferation and invasion, whereas knockdown of miR-381-3p promoted cell proliferation and invasion in MDA-MB-231 and SKBR3 cells. Mechanistically, overexpression of miR-381-3p inhibited breast cancer epithelial-mesenchymal transition (EMT). Both Sox4 and Twist1 were confirmed as targets of miR-381-3p. Moreover, transforming growth factor-β (TGF-β) could reverse the effects of miR-381-3p on breast cancer progression.

Conclusions: Our observation suggests that miR-381-3p inhibits breast cancer progression and EMT by regulating the TGF-β signaling via targeting Sox4 and Twist1.

Keywords: Breast cancer; Epithelial; Mesenchymal transition; Progression; Transforming growth factor-β; miR-381-3p.

MeSH terms

  • Breast Neoplasms* / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Nuclear Proteins
  • Prognosis
  • SOXC Transcription Factors
  • Twist-Related Protein 1

Substances

  • MIRN381 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • SOX4 protein, human
  • SOXC Transcription Factors
  • TWIST1 protein, human
  • Twist-Related Protein 1