Here, we report a novel phenomenon of translational activation of prokaryotic gene expression with trans-acting antisense oligonucleotides targeting the coding region of mRNA. Screening of antisense oligonucleotides complementary to the coding sequences of GFP or ZsGreen identified antisense sequences that activate translation of the mRNAs in a concentration-dependent P005091 purchase manner. We also found that the translational activation highly depends on the hybridization positions of the antisense strands. Translation-activating
antisense oligonucleotides (TAOs) tended to bind to the 5′-region rather than the 3′-region of the mRNA coding region. RNA folding simulation suggested that
TAOs may disrupt the structured elements around the translation initiation region (TIR) by pairing with complementary sequences in the mRNA coding region, resulting in an increase in translation efficiency. Further, we demonstrate that number and position of locked nucleic acid (LNA) bases in the antisense strands govern the tendency of up- or down-regulation. Our findings described here may lead to the discovery of a new class of antisense sRNA and the development of a tool for activating desired gene expression in the future. (C) 2012 Elsevier Inc. All rights reserved.”
“The prognostic relevance of estrogen (ER) and progesterone receptor (PR) expression in endometrioid endometrial cancer is still controversially discussed. The present GSI-IX study has focused on the evaluation of the prognostic value SN-38 ic50 of ER alpha, ER beta 1, ER beta 2, and PR in this histotype. Specifically, we were interested in evaluating whether the relative level of ER subtype-specific expression (in terms of a ratio ER alpha/ER beta 1 and
ER alpha/ER beta 2) would predict clinical outcome better than their absolute levels in patients with endometrioid endometrial cancer. To this end, protein content was assessed by immunohistochemistry in a group of 121 cases and staining was analyzed in relation to clinicopathologic variables, disease-free survival and overall survival. Results obtained have demonstrated that none of the biological markers analyzed possess an independent prognostic role with regard to disease-free survival. Multivariate analysis of overall survival has shown that ER alpha alone is not an independent prognostic indicator in patients with endometrioid endometrial cancer (hazard ratio [HR]; 0.5; 95% confidence interval [CI], 0.09-3.0; P = .5). On the other hand, an ER alpha/ER beta 1 ratio of 1 or less or an ER alpha/ER beta 2 ratio of 1 or less has proved to be independently associated with a higher risk of death (HR, 6.4 [95% CI, 1.0-40.6; P = .04] and 9.7 [95% CI, 1.1-85.3; P = .04], respectively) along with age, tumor stage, and Ki-67.