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Mol Cancer. 2019 Jan 22;18(1):15. doi: 10.1186/s12943-019-0942-1.

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

Author information

1
Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
2
Department of Cardiology, KaiFeng Central Hospital, KaiFeng, Henan Province, China.
3
Department of Venous Injection Distribution Center, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
4
School of Life Science and Technology, Harbin Institute of Technology, Harbin, People's Republic of China.
5
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China. zhangdaming@ymail.com.
6
Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China. doctorcheng77@163.com.

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.

KEYWORDS:

Long noncoding RNA; OTUD6B-AS1; Proliferation; Wnt/β-catenin signaling; ccRCC

PMID:
30670025
PMCID:
PMC6341572
DOI:
10.1186/s12943-019-0942-1
[Indexed for MEDLINE]
Free PMC Article

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