Changes in the Metastatic Properties of MDA-MB-231 Cells after IGFBP6 Gene Knockdown Is Associated with Increased Expression of miRNA Genes Controlling INSR, IGF1R, and CCND1 Genes

Bull Exp Biol Med. 2019 Mar;166(5):641-645. doi: 10.1007/s10517-019-04409-z. Epub 2019 Mar 22.

Abstract

Metastatic cascade is associated with the process of epithelial-mesenchymal transition accompanied by changes in cell proliferation, migration, adhesion, and invasiveness mediated by the insulin-like growth factor (IGF) signal pathway. IGFBP6 protein binds IGF and prevents its interaction with receptors. IGFBP6 gene knockdown through RNA-interference inhibits cell migration and increased the rate of proliferation of breast cancer MDA-MB-231 cells. IGFBP6 knockdown cells are characterized by increased expression of MIR100 and MIRLET7A2 genes encoding hsa-miR-100-3p, hsa-miR-100-5p, hsa-let-7a-5p, and hsa-let-7a-2-3p miRNA. The target genes of these microRNAs are IGF2, IGF1R, INSR, and CCND1 associated with IGF signaling pathway and proliferative and migratory activity during the metastatic cascade. A significant decrease in the expression of INSR and CCND1 genes was demonstrated by PCR and microarray analysis.

Keywords: IGFBP6; MDA-MB-231; breast cancer; epithelial-mesenchymal transition; metastasis cascade.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Receptor, IGF Type 1
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism*
  • Receptors, Somatomedin / genetics
  • Receptors, Somatomedin / metabolism*

Substances

  • Antigens, CD
  • CCND1 protein, human
  • IGF1R protein, human
  • MicroRNAs
  • Receptors, Somatomedin
  • Cyclin D1
  • INSR protein, human
  • Receptor, IGF Type 1
  • Receptor, Insulin