MiR-519d-3p suppresses breast cancer cell growth and motility via targeting LIM domain kinase 1

Mol Cell Biochem. 2018 Jul;444(1-2):169-178. doi: 10.1007/s11010-017-3241-4. Epub 2017 Nov 29.


Breast cancer is the most common female cancer in women, and its estrogen receptor (ER)-negative subtype (ENBC) and triple-negative subtype (TNBC) have unfavorable prognosis in comparison with ER-positive subtype. MiRNAs are small noncoding RNAs that bind to the 3'-UTR region of targeting mRNAs to regulate gene expression. Mir-519d-3p was found to be associated with breast cancer for its potential role in proliferation and metastasis. To explore its potential role and mechanism of miR-519d-3p in breast carcinogenesis, we determined whether miR-519d-3p regulates breast cancer cell proliferation and motility by performing wound-healing assays and migration-invasion assays. We found that miR-519d-3p significantly inhibits proliferation and motility of ENBC and TNBC cells. Overexpression of miR-519d-3p arrested breast cancer cells in the G0/G1 phase and reduced the expression of CDK4, 6/Cyclin D1, and CDK2/Cyclin E1. It was reported that miR-519d-3p or miR-519d-3p expression was associated with cancer metastasis and clinical staging. Since LIM domain kinase 1 (LIMK1) was highly expressed in breast cancer and a major regulator of breast cancer growth and metastasis, we further demonstrated that LIMK1 is a potential target of miR-519d-3p by dual-luciferase report assay. Mir-519d-3p decreases LIMK1 expression at mRNA and protein levels, and the protein level and phosphorylation of cofilin 1 (CFL1), one of the key downstream targets of LIMK1. Our findings suggest that miR-519d-3p regulates the LIMK1/CFL1 pathway in breast cancer and this new venue could be targeted for future breast cancer therapy.

Keywords: Breast cancer; Cofilin 1; LIM domain kinase 1; Metastasis; MiR-519d-3p; Proliferation.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Female
  • HEK293 Cells
  • Humans
  • Lim Kinases / genetics
  • Lim Kinases / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*


  • MIRN519 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • LIMK1 protein, human
  • Lim Kinases