Identification of ZNF217, hnRNP‐K, VEGF‐A and IPO7 as targets for microRNAs that are downregulated in prostate carcinoma. Issue 4 (3rd August 2012)

• Record Type: Journal Article
• Authors: Szczyrba, Jaroslaw; Nolte, Elke; Hart, Martin; Döll, Celina; Wach, Sven; Taubert, Helge; Keck, Bastian; Kremmer, Elisabeth; Stöhr, Robert; Hartmann, Arndt; Wieland, Wolf; Wullich, Bernd; Grässer, Friedrich A.
• Is Part Of: International journal of cancer. Volume 132:Issue 4(2013:Feb. 15)
• Page Start: 775
• Page End: 784
• Publication Date: 2012-08-03
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.27731
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>In primary prostate cancer (PCa), a major cause of cancer‐related death in men, the expression of various microRNAs (miRNAs) is deregulated. We previously detected several miRNAs, for example, <italic>miR‐24 and miR‐22</italic>, as significantly downregulated in PCa (Szczyrba et al., Mol Cancer Res 2010;8:529‐38). An <italic>in silico</italic> search predicted that zinc finger protein 217 (<italic>ZNF217</italic>) and importin 7 (<italic>IPO7</italic>) were potential target genes of these miRNAs. Additionally, for two genes that are deregulated in PCa (heterogeneous nuclear ribonucleoprotein K, <italic>hnRNP‐K, and</italic> vascular endothelial growth factor A, <italic>VEGF‐A</italic>), we identified two regulatory miRNAs, <italic>miR‐205</italic> and <italic>miR‐29b</italic>. The regulation of the 3′‐untranslated regions of the four genes by their respective miRNAs was confirmed by luciferase assays. As expected, the upregulation of <italic>ZNF217</italic>, <italic>hnRNP‐K</italic>, <italic>VEGF‐A</italic> and <italic>IPO7</italic> could be verified at the protein level in the PCa cell lines LNCaP and DU145. <italic>ZNF217</italic> and <italic>IPO7</italic>, which had not yet been studied in PCa, were analyzed in more detail. <italic>ZNF217</italic> mRNA is overexpressed in primary PCa samples, and this overexpression translates to an elevated protein level. However, <italic>IPO7</italic> was upregulated at the protein level alone. The inhibition of <italic>ZNF217</italic> and <italic>IPO7</italic> by siRNA resulted in reduced proliferation of the PCa cell lines. <italic>ZNF217</italic> could thus be identified as an oncogene that is overexpressed in PCa and affects the growth of PCa cell lines, whereas the function of <italic>IPO7</italic> remains to be elucidated in greater detail.</p> </abstract>