Molecular mechanism of miR-153 inhibiting migration, invasion and epithelial-mesenchymal transition of breast cancer by regulating transforming growth factor beta (TGF-β) signaling pathway

J Cell Biochem. 2019 Jun;120(6):9539-9546. doi: 10.1002/jcb.28230. Epub 2018 Dec 7.


Objective: To investigate the role and mechanism of action of miR-153 in the migration, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells.

Methods: Quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-153 and transforming growth factor beta receptor 2 (TGFBR2) in tissue specimens and cells. miR-153 overexpression in breast cancer cells was achieved by miR-153 mimic transfection. Mobility and invasiveness of breast cancer cells were evaluated by transwell assay. EMT was evaluated by Western blot detecting the protein level of E-cadherin and Vimentin. Interaction of miR-153 and 3'-untranslated region (UTR) of TGFBR2 messenger RNA (mRNA) was investigated by luciferase reporter assay.

Results: The expression of miR-153 in breast cancer tissue specimens and MDA-MB-231 cells was significantly lower than that in nonmalignant counterparts, inversely correlating with that of TGFBR2 mRNA. Transfection with miR-153 mimic significantly increased miR-153 level in MDA-MB-231 cells while inhibiting its migration, invasion, and EMT in vitro, which could be mimicked by TGFBR2 knockdown. Luciferase reporter assay confirmed two targets of miR-153 on the 3'-UTR of TGFBR2 mRNA. Restoring TGFBR2 protein level by transient overexpression largely rescued migration, invasion, and EMT of MDA-MB-231 cells that were repressed by miR-153 mimic transfection.

Conclusion: miR-153 inhibits breast cancer cell migration, invasion, and EMT by targeting TGFBR2.

Keywords: epithelial-mesenchymal transition (EMT); invasion; miR-153; migration; transforming growth factor beta receptor 2 (TGFBR2).

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Transforming Growth Factor-beta Type II / genetics
  • Receptor, Transforming Growth Factor-beta Type II / metabolism
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation / genetics


  • MIRN153 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Receptor, Transforming Growth Factor-beta Type II