The proto‐oncogene ERG is a target of microRNA miR‐145 in prostate cancer. (8th April 2013)

• Record Type: Journal Article
• Authors: Hart, Martin; Wach, Sven; Nolte, Elke; Szczyrba, Jaroslaw; Menon, Roopika; Taubert, Helge; Hartmann, Arndt; Stoehr, Robert; Wieland, Wolf; Grässer, Friedrich A.; Wullich, Bernd
• Is Part Of: FEBS journal. Volume 280:Number 9(2013)
• Page Start: 2105
• Page End: 2116
• Publication Date: 2013-04-08
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.12236
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs12236-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Prostate cancer is a leading cause of cancer mortality in men. One of the distinct characteristics of prostate cancer is over‐expression of the <italic>ERG</italic> proto‐oncogene. The <italic>TMPRSS2–ERG</italic> gene fusion, the most common gene fusion, is found in approximately 50% of prostate cancer cases. We show that certain microRNAs are extensively deregulated in prostate cancer cell lines and primary clinical cancer samples. MicroRNAs are capable of modulating post‐transcriptional gene expression via inhibition of protein synthesis. Independent target prediction methods have indicated that the 3′ untranslated region of the <italic>ERG</italic> mRNA is a potential target of <italic>miR‐145</italic>. <italic>miR‐145</italic> is consistently down‐regulated in prostate cancer. Here we show that the <italic>ERG</italic> 3′ untranslated region is a regulative target of <italic>miR‐145 in vitro</italic>. Ectopic expression of <italic>miR‐145</italic> led to a reduction in expression of the ERG protein. We analyzed 26 prostate cancer samples and corresponding normal tissue. ERG protein expression was found to be elevated in the tumor samples, together with increased expression of several ERG isoforms. We identified ERG proteins of 35 and 24 kDa, which may represent unknown <italic>ERG</italic> splice variants. Analyses of <italic>miR‐145</italic> and <italic>ERG</italic> mRNA expression revealed a general down‐regulation of <italic>miR‐145</italic> irrespective of the presence or absence of translocations involving <italic>ERG</italic>. This observation indicates that down‐regulation of <italic>miR‐145</italic> may contribute to the increased expression of most <italic>ERG</italic> splice variants sharing the <italic>miR‐145</italic> target sequence in their 3′ untranslated region.</p> </abstract>