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Bulletin of Experimental Biology and Medicine

, Volume 166, Issue 5, pp 641–645 | Cite as

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

  • A. A. PoloznikovEmail author
  • S. V. Nikulin
  • M. P. Raigorodskaya
  • K. A. Fomicheva
  • G. S. Zakharova
  • Yu. A. Makarova
  • B. Ya. Alekseev
GENETICS
  • 9 Downloads

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.

Key Words

IGFBP6 MDA-MB-231 breast cancer metastasis cascade epithelial-mesenchymal transition 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • A. A. Poloznikov
    • 1
    Email author
  • S. V. Nikulin
    • 2
  • M. P. Raigorodskaya
    • 2
  • K. A. Fomicheva
    • 1
  • G. S. Zakharova
    • 2
  • Yu. A. Makarova
    • 1
  • B. Ya. Alekseev
    • 1
  1. 1.A. F. Tsyb Medical Radiological Research Center, National Medical Research Radiological Center of the Ministry of Health of the Russian FederationObninskRussia
  2. 2.BioClinicum Research CenterMoscowRussia

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