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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bill R, Christofori G. The relevance of EMT in breast cancer metastasis: Correlation or causality? FEBS Lett. 2015;589(14):1577-1587.
Chou CH, Shrestha S, Yang CD, Chang NW, Lin YL, Liao KW, Huang WC, Sun TH, Tu SJ, Lee WH, Chiew MY, Tai CS, Wei TY, Tsai TR, Huang HT, Wang CY, Wu HY, Ho SY, Chen PR, Chuang CH, Hsieh PJ, Wu YS, Chen WL, Li MJ, Wu YC, Huang XY, Ng FL, Buddhakosai W, Huang PC, Lan KC, Huang CY, Weng SL, Cheng YN, Liang C, Hsu WL, Huang HD. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. 2018;46(D1):D296-D302.
Ernst AK, Putscher A, Samatov TR, Suling A, Galatenko VV, Shkurnikov MY, Knyazev EN, Tonevitsky AG, Haalck T, Lange T, Maar H, Schröder-Schwarz J, Riecken K, Schumacher U, Wicklein D. Knockdown of L1CAM significantly reduces metastasis in a xenograft model of human melanoma: L1CAM is a potential target for anti-melanoma therapy. PLoS One. 2018;13(2):e0192525. doi: https://doi.org/10.1371/journal.pone.0192525.
Fomicheva KA, Osip’yants AI, Knyazev EN, Samatov TR, Shkurnikov MY. Detection of potential metastatic prostate cancer circulating biomarkers by comparison of miRNA profiles in DU145 cells and culture medium. Bull. Exp. Biol. Med. 2017;162(6):792-796.
Fusté NP, Fernández-Hernández R, Cemeli T, Mirantes C, Pedraza N, Rafel M, Torres-Rosell J, Colomina N, Ferrezuelo F, Dolcet X, Garí E. Cytoplasmic cyclin D1 regulates cell invasion and metastasis through the phosphorylation of paxillin. Nat. Commun. 2016;7. ID 11581. doi: https://doi.org/10.1038/ncomms11581.
Gandellini P, Doldi V, Zaffaroni N. microRNAs as players and signals in the metastatic cascade: Implications for the development of novel anti-metastatic therapies. Semin. Cancer Biol. 2017;44:132-140.
Karagkouni D, Paraskevopoulou MD, Chatzopoulos S, Vlachos IS, Tastsoglou S, Kanellos I, Papadimitriou D, Kavakiotis I, Maniou S, Skoufos G, Vergoulis T, Dalamagas T, Hatzigeorgiou AG. DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA-gene interactions. Nucleic Acids Res. 2018;46(D1):D239-D245.
Knyazev EN, Nyushko KM, Alekseev BY, Samatov TR, Shkurnikov MY. Suppression of ITGB4 gene expression in PC-3 cells with short interfering RNA induces changes in the expression of β-integrins associated with RGD-receptors. Bull. Exp. Biol. Med. 2015;159(4):541-545.
Makarova JA, Shkurnikov MU, Wicklein D, Lange T, Samatov TR, Turchinovich AA, Tonevitsky AG. Intracellular and extracellular microRNA: an update on localization and biological role. Prog. Histochem. Cytochem. 2016;51(3-4):33-49.
Nikulin SV, Raigorodskaya MP, Poloznikov AA, Zakharova GS, Schumacher U, Wicklein D, Stürken C, Riecken K, Fomicheva KA, Alekseev BY, Shkurnikov MY. Role of IGFBP6 Protein in the Regulation of Epithelial-Mesenchymal Transition Genes. Bull. Exp. Biol. Med. 2018;164(5):650-654.
Nikulin SV, Raigorodskaya MP, Poloznikov AA, Zakharova GS, Schumacher U, Wicklein D, Stürken C, Riecken K, Fomicheva KA, Alekseev BY, Shkurnikov MY. In Vitro model for studying of the role of IGFBP6 gene in breast cancer metastasizing. Bull. Exp. Biol. Med. 2018;164(5):688-692.
Poloz Y, Dowling RJO, Stambolic V. Fundamental pathways in breast cancer 1: signaling from the membrane. Breast Cancer. Veronesi U, Goldhirsch A, Veronesi P, Gentilini OD, Leonardi MC, eds. Cham, 2017. P. 3-12.
Rudimov EG, Knjazev EN, Khaustova NA, Grigorieva OV, Buravkova LB. Transcriptomic changes in human umbilical cord blood endothelial cells under simulated microgravity. Dokl. Biochem. Biophys. 2017;472(1):1-4.
Shkurnikov MY, Knyazev EN, Wicklein D, Schumacher U, Samatov TR, Tonevitskii AG. Role of L1CAM in the regulation of the canonical Wnt pathway and class I MAGE genes. Bull. Exp. Biol. Med. 2016;160(6):807-810.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 166, No. 11, pp. 587-591, November, 2018
Rights and permissions
About this article
Cite this article
Poloznikov, A.A., Nikulin, S.V., Raigorodskaya, M.P. et al. 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 166, 641–645 (2019). https://doi.org/10.1007/s10517-019-04409-z
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-019-04409-z