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长链非编码RNA牛磺酸上调基因1的敲低通过Wnt/β-连环蛋白通路抑制膀胱尿路上皮癌对阿霉素的耐药性。

Knockdown of long non-coding RNA Taurine Up-Regulated 1 inhibited doxorubicin resistance of bladder urothelial carcinoma via Wnt/β-catenin pathway.

作者信息

Xie Dalong, Zhang Hui, Hu Xuanhao, Shang Chao

机构信息

Department of Anatomy, College of Basic Medicine, China Medical University, Shenyang, 110001, China.

Department of Urinary surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, China.

出版信息

Oncotarget. 2017 Sep 15;8(51):88689-88696. doi: 10.18632/oncotarget.20927. eCollection 2017 Oct 24.

Abstract

In genitourinary system, bladder cancer (BC) is the most common and lethal malignant tumor, which most common type is bladder urothelial carcinoma (BUC). Long non-coding RNA (lncRNA) Taurine Up-Regulated 1 (TUG1) gene is high-expressed in several malignant tumors, including BC. In this study, over-expression of TUG1 was found in BUC tissues and cell line resistant to doxorubicin (Dox). Knockdown of TUG1 inhibited the Dox resistance and promoted the cytotoxicity induced by Dox in T24/Dox cells. TUG1 knockdown also depressed the Wnt/β-catenin pathway, and the activation the Wnt/β-catenin pathway partly reversed the inhibitory effects of TUG1 knockdown on Dox resistance in T24/Dox cells. In conclusion, up-regulation of lncRNA TUG1 was related with the poor response of BUC patients to Dox chemotherapy, knockdown of TUG1 inhibited the Dox resistance of BUC cells via Wnt/β-catenin pathway. These findings might assist in the discovery of novel potential diagnostic and therapeutic target for BUC, thereby improve the effects of clinical treatment in patients.

摘要

在泌尿生殖系统中,膀胱癌(BC)是最常见且致命的恶性肿瘤,其最常见的类型是膀胱尿路上皮癌(BUC)。长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)在包括BC在内的多种恶性肿瘤中高表达。在本研究中,在BUC组织和对阿霉素(Dox)耐药的细胞系中发现TUG1过表达。敲低TUG1可抑制T24/Dox细胞对Dox的耐药性并增强Dox诱导的细胞毒性。TUG1敲低还可抑制Wnt/β-连环蛋白信号通路,而激活该信号通路可部分逆转TUG1敲低对T24/Dox细胞Dox耐药性的抑制作用。总之,lncRNA TUG1的上调与BUC患者对Dox化疗反应不佳有关,敲低TUG1可通过Wnt/β-连环蛋白信号通路抑制BUC细胞的Dox耐药性。这些发现可能有助于发现BUC新的潜在诊断和治疗靶点,从而提高患者的临床治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bd/5687637/0037dc120f17/oncotarget-08-88689-g001.jpg

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