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
- Authors: Poloznikov A.A.1, Nikulin S.V.2, Raigorodskaya M.P.2, Fomicheva K.A.1, Zakharova G.S.2, Makarova Y.A.1, Alekseev B.Y.1
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Affiliations:
- A. F. Tsyb Medical Radiological Research Center, National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
- BioClinicum Research Center
- Issue: Vol 166, No 5 (2019)
- Pages: 641-645
- Section: Genetics
- URL: https://journals.rcsi.science/0007-4888/article/view/241248
- DOI: https://doi.org/10.1007/s10517-019-04409-z
- ID: 241248
Cite item
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.
About the authors
A. A. Poloznikov
A. F. Tsyb Medical Radiological Research Center, National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
Author for correspondence.
Email: andrey.poloznikov@nmicr.ru
Russian Federation, Obninsk, Moscow Region
S. V. Nikulin
BioClinicum Research Center
Email: andrey.poloznikov@nmicr.ru
Russian Federation, Moscow
M. P. Raigorodskaya
BioClinicum Research Center
Email: andrey.poloznikov@nmicr.ru
Russian Federation, Moscow
K. A. Fomicheva
A. F. Tsyb Medical Radiological Research Center, National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
Email: andrey.poloznikov@nmicr.ru
Russian Federation, Obninsk, Moscow Region
G. S. Zakharova
BioClinicum Research Center
Email: andrey.poloznikov@nmicr.ru
Russian Federation, Moscow
Yu. A. Makarova
A. F. Tsyb Medical Radiological Research Center, National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
Email: andrey.poloznikov@nmicr.ru
Russian Federation, Obninsk, Moscow Region
B. Ya. Alekseev
A. F. Tsyb Medical Radiological Research Center, National Medical Research Radiological Center of the Ministry of Health of the Russian Federation
Email: andrey.poloznikov@nmicr.ru
Russian Federation, Obninsk, Moscow Region