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. Poloznikov, S. V. Nikulin, M. P. Raigorodskaya, K. A. Fomicheva, G. S. Zakharova, Yu A. Makarova, B. Ya Alekseev

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)641-645
Number of pages5
JournalBulletin of Experimental Biology and Medicine
Volume166
Issue number5
DOIs
StatePublished - 15 Mar 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

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

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