High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma
ObjectiveThis study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC).MethodsCitron kinase (CIT) expression in ESCC tissues was analyzed based on the microarray dataset GSE20347, and CIT expression in ESCC cell lines...
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| Format: | Article |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.628547/full |
| _version_ | 1818737740983828480 |
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| author | Wenfeng Lu Yun Dong Qing Cui Yuhan Wang Xiwen Yang Xiaoyue Cai Ming Zhang |
| author_facet | Wenfeng Lu Yun Dong Qing Cui Yuhan Wang Xiwen Yang Xiaoyue Cai Ming Zhang |
| author_sort | Wenfeng Lu |
| collection | DOAJ |
| description | ObjectiveThis study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC).MethodsCitron kinase (CIT) expression in ESCC tissues was analyzed based on the microarray dataset GSE20347, and CIT expression in ESCC cell lines was analyzed. Eca-109 cells were lentivirally transfected with shRNA-CIT (LV-shCIT) to knock down CIT, followed by investigation of cell proliferation and apoptosis. Nude mouse xenograft experiments were performed to evaluate the tumorigenicity of CIT-knockdown Eca-109 cells. Microarray analysis of Eca-109 cells transfected with LV-shCIT or LV-shNC and subsequent Ingenuity Pathway Analysis (IPA) were performed to identify CIT-related differentially expressed genes (DEGs) and signaling pathways. Furthermore, the expression of key DEGs was validated using the clinical samples of ESCC.ResultsCitron kinase (CIT) was highly expressed in ESCC tissues and cell lines. Knockdown of CIT suppressed Eca-109 cell proliferation and promoted apoptosis in vitro. Moreover, CIT knockdown significantly reduced tumorigenicity of Eca-109 cells in vivo. Microarray and IPA analysis showed that signaling by the Rho family GTPases pathway was significantly activated, and CIT intrinsically interacted with the protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), sequestosome 1 (SQSTM1), and interleukin 6 (IL6). Notably, the expression levels of PRKAA1 and SQSTM1 were upregulated in ESCC tissues, while the IL6 expression was downregulated.ConclusionOur findings confirm that CIT functions as an oncogene in ESCC. CIT may contribute to ESCC development by upregulating PRKAA1 and SQSTM1 as well as downregulating IL6. Citron kinase may serve as a promising therapeutic target for ESCC. |
| first_indexed | 2024-12-18T00:57:51Z |
| format | Article |
| id | doaj.art-022b8c0320044dd6a599aaa66a0d3bbd |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-18T00:57:51Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-022b8c0320044dd6a599aaa66a0d3bbd2022-12-21T21:26:26ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-07-011210.3389/fgene.2021.628547628547High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell CarcinomaWenfeng Lu0Yun Dong1Qing Cui2Yuhan Wang3Xiwen Yang4Xiaoyue Cai5Ming Zhang6Department of Integrative Medicine, Zhongshan Hospital and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai, ChinaDepartment of Integrative Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Integrative Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Integrative Medicine, Zhongshan Hospital and Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, Shanghai, ChinaDepartment of Integrative Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Integrative Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Integrative Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaObjectiveThis study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC).MethodsCitron kinase (CIT) expression in ESCC tissues was analyzed based on the microarray dataset GSE20347, and CIT expression in ESCC cell lines was analyzed. Eca-109 cells were lentivirally transfected with shRNA-CIT (LV-shCIT) to knock down CIT, followed by investigation of cell proliferation and apoptosis. Nude mouse xenograft experiments were performed to evaluate the tumorigenicity of CIT-knockdown Eca-109 cells. Microarray analysis of Eca-109 cells transfected with LV-shCIT or LV-shNC and subsequent Ingenuity Pathway Analysis (IPA) were performed to identify CIT-related differentially expressed genes (DEGs) and signaling pathways. Furthermore, the expression of key DEGs was validated using the clinical samples of ESCC.ResultsCitron kinase (CIT) was highly expressed in ESCC tissues and cell lines. Knockdown of CIT suppressed Eca-109 cell proliferation and promoted apoptosis in vitro. Moreover, CIT knockdown significantly reduced tumorigenicity of Eca-109 cells in vivo. Microarray and IPA analysis showed that signaling by the Rho family GTPases pathway was significantly activated, and CIT intrinsically interacted with the protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), sequestosome 1 (SQSTM1), and interleukin 6 (IL6). Notably, the expression levels of PRKAA1 and SQSTM1 were upregulated in ESCC tissues, while the IL6 expression was downregulated.ConclusionOur findings confirm that CIT functions as an oncogene in ESCC. CIT may contribute to ESCC development by upregulating PRKAA1 and SQSTM1 as well as downregulating IL6. Citron kinase may serve as a promising therapeutic target for ESCC.https://www.frontiersin.org/articles/10.3389/fgene.2021.628547/fullesophageal squamous cell carcinomacitron kinasecell proliferationapoptosistumorigenicity |
| spellingShingle | Wenfeng Lu Yun Dong Qing Cui Yuhan Wang Xiwen Yang Xiaoyue Cai Ming Zhang High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma Frontiers in Genetics esophageal squamous cell carcinoma citron kinase cell proliferation apoptosis tumorigenicity |
| title | High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma |
| title_full | High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma |
| title_fullStr | High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma |
| title_full_unstemmed | High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma |
| title_short | High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma |
| title_sort | high expression of citron kinase contributes to the development of esophageal squamous cell carcinoma |
| topic | esophageal squamous cell carcinoma citron kinase cell proliferation apoptosis tumorigenicity |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.628547/full |
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