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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

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

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. More... »

PAGES

15

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12943-019-0942-1

    DOI

    http://dx.doi.org/10.1186/s12943-019-0942-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111593632

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30670025


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