DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma
Abstract Background Emerging evidence has highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumor development and progression. However, the biological functions and underlying mechanisms of DLEU1 in esophageal squamous cell carcinoma (ESCC) remain unclear. Methods LncRNA expression...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03449-w |
| _version_ | 1828796132840439808 |
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| author | Qihang Li Zhiyu Zhang HongChao Jiang Jun Hou Yuhang Chai Hongxing Nan Feng Li Lianghai Wang |
| author_facet | Qihang Li Zhiyu Zhang HongChao Jiang Jun Hou Yuhang Chai Hongxing Nan Feng Li Lianghai Wang |
| author_sort | Qihang Li |
| collection | DOAJ |
| description | Abstract Background Emerging evidence has highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumor development and progression. However, the biological functions and underlying mechanisms of DLEU1 in esophageal squamous cell carcinoma (ESCC) remain unclear. Methods LncRNA expression in ESCC tissues was explored using lncRNA microarray datasets. The functional roles of DLEU1 in ESCC were demonstrated by a series of in vitro and in vivo experiments. RNA pull-down and immunoprecipitation assays were performed to demonstrate the potential mechanisms of DLEU1. Results In a screen for differentially expressed lncRNAs in ESCC, we determined that DLEU1 was one of the most overexpressed lncRNAs in ESCC tissues and that upregulated DLEU1 expression was associated with a worse prognosis. Functional assays showed that DLEU1 promoted tumor growth by inhibiting cell apoptosis. Mechanistically, DLEU1 could bind and stabilize DYNLL1 by interfering with RNF114-mediated ubiquitination and proteasomal degradation. The DLEU1/DYNLL1 axis subsequently upregulated antiapoptotic BCL2 and promoted cell survival. Furthermore, DLEU1 upregulation was at least partly facilitated by promoter hypomethylation. Notably, targeting DLEU1 sensitized ESCC cells to cisplatin-induced death. Conclusions Our findings suggest that DLEU1-mediated stabilization of DYNLL1 is critical for cell survival and that the DLEU1/DYNLL1 axis may be a promising therapeutic target for ESCC. |
| first_indexed | 2024-12-12T04:16:11Z |
| format | Article |
| id | doaj.art-88465264937644dc851e3e78dd4ad057 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-12T04:16:11Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-88465264937644dc851e3e78dd4ad0572022-12-22T00:38:26ZengBMCJournal of Translational Medicine1479-58762022-05-0120111510.1186/s12967-022-03449-wDLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinomaQihang Li0Zhiyu Zhang1HongChao Jiang2Jun Hou3Yuhang Chai4Hongxing Nan5Feng Li6Lianghai Wang7Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineDepartment of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical UniversityDepartment of Pathology and Medical Research Center, Beijing Chaoyang Hospital, Capital Medical UniversityKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of MedicineAbstract Background Emerging evidence has highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumor development and progression. However, the biological functions and underlying mechanisms of DLEU1 in esophageal squamous cell carcinoma (ESCC) remain unclear. Methods LncRNA expression in ESCC tissues was explored using lncRNA microarray datasets. The functional roles of DLEU1 in ESCC were demonstrated by a series of in vitro and in vivo experiments. RNA pull-down and immunoprecipitation assays were performed to demonstrate the potential mechanisms of DLEU1. Results In a screen for differentially expressed lncRNAs in ESCC, we determined that DLEU1 was one of the most overexpressed lncRNAs in ESCC tissues and that upregulated DLEU1 expression was associated with a worse prognosis. Functional assays showed that DLEU1 promoted tumor growth by inhibiting cell apoptosis. Mechanistically, DLEU1 could bind and stabilize DYNLL1 by interfering with RNF114-mediated ubiquitination and proteasomal degradation. The DLEU1/DYNLL1 axis subsequently upregulated antiapoptotic BCL2 and promoted cell survival. Furthermore, DLEU1 upregulation was at least partly facilitated by promoter hypomethylation. Notably, targeting DLEU1 sensitized ESCC cells to cisplatin-induced death. Conclusions Our findings suggest that DLEU1-mediated stabilization of DYNLL1 is critical for cell survival and that the DLEU1/DYNLL1 axis may be a promising therapeutic target for ESCC.https://doi.org/10.1186/s12967-022-03449-wlncRNAApoptosisUbiquitinationRNF114BCL2 |
| spellingShingle | Qihang Li Zhiyu Zhang HongChao Jiang Jun Hou Yuhang Chai Hongxing Nan Feng Li Lianghai Wang DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma Journal of Translational Medicine lncRNA Apoptosis Ubiquitination RNF114 BCL2 |
| title | DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma |
| title_full | DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma |
| title_fullStr | DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma |
| title_full_unstemmed | DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma |
| title_short | DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma |
| title_sort | dleu1 promotes cell survival by preventing dynll1 degradation in esophageal squamous cell carcinoma |
| topic | lncRNA Apoptosis Ubiquitination RNF114 BCL2 |
| url | https://doi.org/10.1186/s12967-022-03449-w |
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