The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5
Abstract Background The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). However, its underlying mechanisms in the progression of CRC have not been well studied. Methods To investigate the clinical significance of NEA...
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-018-0656-7 |
| _version_ | 1811325823718785024 |
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| author | Meng Zhang Weiwei Weng Qiongyan Zhang Yong Wu Shujuan Ni Cong Tan Midie Xu Hui Sun Chenchen Liu Ping Wei Xiang Du |
| author_facet | Meng Zhang Weiwei Weng Qiongyan Zhang Yong Wu Shujuan Ni Cong Tan Midie Xu Hui Sun Chenchen Liu Ping Wei Xiang Du |
| author_sort | Meng Zhang |
| collection | DOAJ |
| description | Abstract Background The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). However, its underlying mechanisms in the progression of CRC have not been well studied. Methods To investigate the clinical significance of NEAT1, we analyzed its expression levels in a publicly available dataset and in 71 CRC samples from Fudan University Shanghai Cancer Center. Functional assays, including the CCK8, EdU, colony formation, wound healing, and Transwell assays, were used to determine the oncogenic role of NEAT1 in human CRC progression. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and Dual-Luciferase Reporter Assays were used to determine the mechanism of NEAT1 in CRC progression. Animal experiments were used to determine the role of NEAT1 in CRC tumorigenicity and metastasis in vivo. Results NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues. Altered NEAT1 expression led to marked changes in proliferation, migration, and invasion of CRC cells both in vitro and in vivo. Mechanistically, we found that NEAT1 directly bound to the DDX5 protein, regulated its stability, and sequentially activated Wnt signaling. Our study showed that NEAT1 indirectly activated the Wnt/β-catenin signaling pathway via DDX5 and fulfilled its oncogenic functions in a DDX5-mediated manner. Clinically, concomitant NEAT1 and DDX5 protein levels negatively correlated with the overall survival and disease-free survival of CRC patients. Conclusions Our findings indicated that NEAT1 activated Wnt signaling to promote colorectal cancer progression and metastasis. The NEAT1/DDX5/Wnt/β-catenin axis could be a potential therapeutic target of pharmacological strategies. |
| first_indexed | 2024-04-13T14:39:27Z |
| format | Article |
| id | doaj.art-15f355275fc04bcdbd215af63b21f190 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-13T14:39:27Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
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| series | Journal of Hematology & Oncology |
| spelling | doaj.art-15f355275fc04bcdbd215af63b21f1902022-12-22T02:42:56ZengBMCJournal of Hematology & Oncology1756-87222018-09-0111111310.1186/s13045-018-0656-7The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5Meng Zhang0Weiwei Weng1Qiongyan Zhang2Yong Wu3Shujuan Ni4Cong Tan5Midie Xu6Hui Sun7Chenchen Liu8Ping Wei9Xiang Du10Department of Pathology, Fudan University Shanghai Cancer CenterDepartment of Pathology, Fudan University Shanghai Cancer CenterDepartment of Pathology, Fudan University Shanghai Cancer CenterInstitute of Pathology, Fudan UniversityDepartment of Pathology, Fudan University Shanghai Cancer CenterDepartment of Pathology, Fudan University Shanghai Cancer CenterDepartment of Pathology, Fudan University Shanghai Cancer CenterDepartment of Pathology, Fudan University Shanghai Cancer CenterDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Pathology, Fudan University Shanghai Cancer CenterDepartment of Pathology, Fudan University Shanghai Cancer CenterAbstract Background The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been reported to be overexpressed in colorectal cancer (CRC). However, its underlying mechanisms in the progression of CRC have not been well studied. Methods To investigate the clinical significance of NEAT1, we analyzed its expression levels in a publicly available dataset and in 71 CRC samples from Fudan University Shanghai Cancer Center. Functional assays, including the CCK8, EdU, colony formation, wound healing, and Transwell assays, were used to determine the oncogenic role of NEAT1 in human CRC progression. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and Dual-Luciferase Reporter Assays were used to determine the mechanism of NEAT1 in CRC progression. Animal experiments were used to determine the role of NEAT1 in CRC tumorigenicity and metastasis in vivo. Results NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues. Altered NEAT1 expression led to marked changes in proliferation, migration, and invasion of CRC cells both in vitro and in vivo. Mechanistically, we found that NEAT1 directly bound to the DDX5 protein, regulated its stability, and sequentially activated Wnt signaling. Our study showed that NEAT1 indirectly activated the Wnt/β-catenin signaling pathway via DDX5 and fulfilled its oncogenic functions in a DDX5-mediated manner. Clinically, concomitant NEAT1 and DDX5 protein levels negatively correlated with the overall survival and disease-free survival of CRC patients. Conclusions Our findings indicated that NEAT1 activated Wnt signaling to promote colorectal cancer progression and metastasis. The NEAT1/DDX5/Wnt/β-catenin axis could be a potential therapeutic target of pharmacological strategies.http://link.springer.com/article/10.1186/s13045-018-0656-7NEAT1lncRNADDX5β-CateninColorectal cancer |
| spellingShingle | Meng Zhang Weiwei Weng Qiongyan Zhang Yong Wu Shujuan Ni Cong Tan Midie Xu Hui Sun Chenchen Liu Ping Wei Xiang Du The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5 Journal of Hematology & Oncology NEAT1 lncRNA DDX5 β-Catenin Colorectal cancer |
| title | The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5 |
| title_full | The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5 |
| title_fullStr | The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5 |
| title_full_unstemmed | The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5 |
| title_short | The lncRNA NEAT1 activates Wnt/β-catenin signaling and promotes colorectal cancer progression via interacting with DDX5 |
| title_sort | lncrna neat1 activates wnt β catenin signaling and promotes colorectal cancer progression via interacting with ddx5 |
| topic | NEAT1 lncRNA DDX5 β-Catenin Colorectal cancer |
| url | http://link.springer.com/article/10.1186/s13045-018-0656-7 |
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