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

Abstract

BackgroundThe 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).MethodsThe 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.ResultsIn 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.ConclusionsTaken 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.Electronic supplementary materialThe online version of this article (10.1186/s12943-019-0942-1) contains supplementary material, which is available to authorized users.

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21

“…It is significantly downregulated in systemic sclerosis skin biopsies (10). In the field of cancer research, Wang and colleague reported 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 levels of OTUD6B-AS1 indirectly correlated with patient survival (11). We reported downregulation of lncRNA OTUD6B-AS1 in thyroid cancer.…”

“…This study demonstrates that the lower expression of OTUD6B-AS1 is associated with poor prognosis of ccRCC (11). In vitro and in vivo evidence indicates that OTUD6B-AS1 functions as a tumor suppressor in ccRCC (11). However, the expressions and biological functions of OTUD6B-AS1 are still unknown in thyroid carcinomas.…”

“…The role of OTUD6B-AS1 in cancer is largely unknown. A recent study reveals the role of OTUD6B-AS1 in clear cell renal cell carcinoma (ccRCC) (11). This study demonstrates that the lower expression of OTUD6B-AS1 is associated with poor prognosis of ccRCC (11).…”

“…A recent study reveals the role of OTUD6B-AS1 in clear cell renal cell carcinoma (ccRCC) (11). This study demonstrates that the lower expression of OTUD6B-AS1 is associated with poor prognosis of ccRCC (11). In vitro and in vivo evidence indicates that OTUD6B-AS1 functions as a tumor suppressor in ccRCC (11).…”

lncRNA SNHG7 affects malignant tumor behaviors through downregulation of EZH2 in uveal melanoma cell lines

“…A number of studies have demonstrated that lncRNAs play a key role in the occurrence and development of different types of tumor (9)(10)(11). Studies have demonstrated that lncRNAs regulate several cancer characteristics, including cell proliferation, apoptosis and invasion (12)(13)(14). lncRNAs are highly valuable for determining the pathological characteristics of different types of tumor, analyzing the prognosis and providing appropriate treatment (15).…”