Data from Downregulation of Sec23A Protein by miRNA-375 in Prostate Carcinoma

Abstract

<div>Abstract<p>Prostate carcinoma (CaP) is a leading cause of cancer-related death in men. We have previously determined the microRNA (miRNA) profile of primary CaP in comparison with nontumor prostate tissue. miRNAs are small, noncoding RNAs that inhibit protein synthesis on a posttranscriptional level by binding to the 3′-untranslated region (3′-UTR) of their target genes. In primary CaP tissue, we have previously found by miRNA sequencing that <i>miR-375</i> and <i>miR-200c</i> were upregulated 9.1- and 4.5-fold, respectively. A computational analysis predicted the 3′-UTR of the <i>SEC23A</i> gene as a potential target for both <i>miR-375</i> and <i>miR-200c</i>. Here, we show that the 3′-UTR of <i>SEC23A</i> mRNA is indeed a target for <i>miR-375</i> and <i>miR-200c</i> and that both miRNAs downregulate Sec23A protein expression when ectopically expressed in human 293T cells. In primary samples of CaP, we found a direct correlation between reduction of <i>SEC23A</i> mRNA and overexpression of <i>miR-375</i> but not of <i>miR-200c</i>. The reduced levels of Sec23A protein were inversely correlated to the increased amount of <i>miR-375</i> in the LNCaP and DU145 CaP cell lines when compared with normal prostate fibroblasts. In primary CaP, we also detected decreased amounts of Sec23A protein when compared with corresponding normal prostate tissue. Ectopically overexpressed Sec23A in LNCaP and DU145 CaP cells significantly reduced the growth properties, indicating that Sec23A might play a role in the induction or growth of prostate carcinoma. Sec23A overexpression reduced cell growth but did not induce apoptosis, whereas inhibition of Sec23A stimulated cell proliferation. <i>Mol Cancer Res; 9(6); 791–800. ©2011 AACR</i>.</p></div>