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

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.

• 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
• Journal: Molecular cancer (Mol Cancer) Vol. 18 Issue 1 Pg. 15 (01 22 2019) ISSN: 1476-4598 [Electronic] England
• PMID: 30670025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTNNB1 protein, human
• RNA, Long Noncoding
• beta Catenin

Topics

• Animals
• Apoptosis (genetics)
• Carcinogenesis (genetics)
• Carcinoma, Renal Cell (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Progression
• Down-Regulation
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Humans
• Kidney Neoplasms (genetics, pathology)
• Mice
• Mice, Nude
• Prognosis
• RNA, Long Noncoding (genetics)
• Wnt Signaling Pathway (genetics)
• beta Catenin (genetics)