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 a...
| Main Authors: | , , , , , , , , , , , , , |
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| Language: | English |
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BMC
2019-01-01
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| Series: | Molecular Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12943-019-0942-1 |
| _version_ | 1819206363774976000 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Gang Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T05:06:25Z |
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| id | doaj.art-3f52e2a49e6746e6b4b0ce4615494467 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-23T05:06:25Z |
| publishDate | 2019-01-01 |
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| spelling | doaj.art-3f52e2a49e6746e6b4b0ce46154944672022-12-21T17:59:04ZengBMCMolecular Cancer1476-45982019-01-0118111510.1186/s12943-019-0942-1Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathwayGang Wang0Zi-jian Zhang1Wen-gang Jian2Pan-hong Liu3Wei Xue4Teng-da Wang5Yu-yang Meng6Chao Yuan7Hao-ming Li8Yi-peng Yu9Zhan-xin Liu10Qiong Wu11Da-ming Zhang12Cheng Zhang13Department of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, KaiFeng Central HospitalDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Venous Injection Distribution Center, The First Affiliated Hospital of Harbin Medical UniversitySchool of Life Science and Technology, Harbin Institute of TechnologyDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Urology, The First Affiliated Hospital of Harbin Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s12943-019-0942-1Long noncoding RNAOTUD6B-AS1ccRCCProliferationWnt/β-catenin signaling |
| spellingShingle | 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 Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway Molecular Cancer Long noncoding RNA OTUD6B-AS1 ccRCC Proliferation Wnt/β-catenin signaling |
| 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 |
| title_full | Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway |
| title_fullStr | Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway |
| title_full_unstemmed | Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway |
| title_short | Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway |
| title_sort | novel long noncoding rna otud6b as1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the wnt β catenin signaling pathway |
| topic | Long noncoding RNA OTUD6B-AS1 ccRCC Proliferation Wnt/β-catenin signaling |
| url | http://link.springer.com/article/10.1186/s12943-019-0942-1 |
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