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.

Highlights

  • In genitourinary system, bladder cancer (BC) is the most common and lethal malignant tumor, which most common type is bladder urothelial carcinoma (BUC)

  • To screen the Long non-coding RNA (lncRNA) associated with Dox resistance in BUC, the 4 Dox (−) and 4 Dox (+) BUC samples were examined with LncRNA array

  • The up-regulation of Taurine Up-Regulated 1 (TUG1) in Dox (−) BUC samples compared with Dox (+) BUC samples was confirmed by the following large sample Quantitative real time PCR (qRT-PCR) assay (Figure 1B)

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Summary

Introduction

Bladder cancer (BC) is the most common and lethal malignant tumor, which most common type is bladder urothelial carcinoma (BUC). Surgical operation is the preferred and key preference for BUC patients, systemic and intravesical chemotherapy may decrease BUC cell metastasis and improve patient survival [1]. Tremendously chemotherapy strategies have been improved recently, but resistance to chemotherapeutics has severely limited the efficacies of these drugs in clinical BUC applications, the prognosis of BUC patients is still poor [2]. It is crucial to elucidate the mechanisms underlying BUC chemoresistance and identifying novel therapeutic targets will be crucial to further improvements in BUC patient prognosis. Accumulating evidences showed that the long noncoding RNAs (lncRNAs) might play important roles in carcinogenesis [3, 4]. With the development of bioinformatics and functional genomics studies, many lncRNAs were discovered reflecting disease progression and serving as a predictor of patient outcomes [8, 9]

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