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Open Access 01-12-2019 | Kidney Cancer | Research

Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway

Authors: Gang Wang, Zi-jian Zhang, Wen-gang Jian, Pan-hong Liu, Wei Xue, Teng-da Wang, Yu-yang Meng, Chao Yuan, Hao-ming Li, Yi-peng Yu, Zhan-xin Liu, Qiong Wu, Da-ming Zhang, Cheng Zhang

Published in: Molecular Cancer | Issue 1/2019

Abstract

Background

The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC).

Methods

The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo.

Results

In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo.

Conclusions

Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.

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Title: Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway
Authors: Gang Wang
Zi-jian Zhang
Wen-gang Jian
Pan-hong Liu
Wei Xue
Teng-da Wang
Yu-yang Meng
Chao Yuan
Hao-ming Li
Yi-peng Yu
Zhan-xin Liu
Qiong Wu
Da-ming Zhang
Cheng Zhang
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Kidney Cancer
Kidney Cancer
Kidney Cancer
Published in: Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-019-0942-1

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Abstract

Background

Methods

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Conclusions

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