220001

VWCE

Upregulated gene 11 (URG11), recently identified as a new HBx-upregulated gene that may activate beta-catenin and Wnt signaling, was found to be upregulated in a human tubule cell line under low oxygen. Here, we investigated the potential role of URG11 in hypoxia-induced renal tubular epithelial-to-mesenchymal (EMT). Overexpression of URG11 in a human proximal tubule cell line (HK2) promoted a mesenchymal phenotype accompanied by reduced expression of the epithelial marker E-cadherin and increased expression of the mesenchymal markers vimentin and alpha-SMA, while URG11 knockdown by siRNA effectively reversed hypoxia-induced EMT. URG11 promoted the expression of beta-catenin and increased its nuclear accumulation under normoxic conditions through transactivation of the beta-catenin promoter. This in turn upregulated beta-catenin/T-cell factor (TCF) and its downstream effector genes, vimentin, and alpha-SMA. In vivo, strong expression of URG11 was observed in the tubular epithelia of 5/6-nephrectomized rats, and a Western blot analysis demonstrated a close correlation between HIF-1alpha and URG11 protein levels. Altogether, our results indicate that URG11 mediates hypoxia-induced EMT through the suppression of E-cadherin and the activation of the beta-catenin/TCF pathway.CI - Copyright 2009 Elsevier Inc. All rights reserved.

The poor prognosis and high recurrent rate of pancreatic cancer (PC) necessitates the discovery of new predictive markers of PC invasion and prognosis. In this study, we evaluated the expression pattern of up-regulated gene 11 (URG11) in a tissue microarray with 18 pairs of PC and adjacent normal tissues. It was shown that URG11 was significantly up-regulated in PC tissues. High expression levels of URG11 were detected in all PC specimens, but were rarely detected in adjacent non-tumorous tissues. In addition, high expression of URG11 was correlated to poor prognosis. Furthermore, it was discovered that URG11 was correlated to epithelial-mesenchymal transition (EMT) markers and clinical pathological parameters indicative of high PC invasion, while knockdown of URG11 significantly changed the expression pattern of EMT markers and decreased the invasion of PC cells. These findings indicate that URG11 might enhance the invasion of PC by inducing EMT and thus lead to poor PC prognosis. Thus, URG11 has the potential to be a new predictive biomarker of PC invasion and prognosis, which may help in the diagnosis and treatment of PC patients.

Upregulated gene 11 (URG11) represents a gene upregulated by hepatitis B virus X protein and is involved in the biological processes of multifarious tumors. The present study aimed to investigate the protective effects and regulatory mechanisms of URG11 in benign prostatic hyperplasia (BPH). URG11, Ras homolog family member A (RhoA) and Rhoassociated protein kinase 1 (ROCK1) expression was detected in patients with BPH using reverse transcriptionquantitative polymerase chain reaction (RTqPCR). Furthermore, URG11 expression was silenced using URG11targeting small interfering RNAs. In addition, cell viability was determined by performing a Cell Counting Kit8 assay, and the effect of URG11 on the cell cycle was investigated by flow cytometry. expression levels of cyclin D1, p27, Ecadherin, Ncadherin, vimentin, RhoA and ROCK1 were investigated by RTqPCR and western blotting. The results revealed that the expression levels of URG11, RhoA and ROCK1 were enhanced in patients with BPH1 cells compared with matched healthy controls. Furthermore, it was demonstrated that transforming growth factorbeta (TGFbeta) induced the proliferation of BPH1 cells in vitro, and silencing of URG11 inhibited the effects of TGFbeta on BPH1 cell proliferation and the cell cycle. In addition, silencing of URG11 altered the expression levels of cell cycleassociated genes, epithelialmesenchymal transitionassociated genes, and RhoA and ROCK1 protein levels. Thus, the results of the present study suggest that URG11 may be a potential therapeutic target, which may be important to inhibit the development and progression of prostatic hyperplasia.