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High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma
OBJECTIVE: This study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC). METHODS: Citron kinase (CIT) expression in ESCC tissues was analyzed based on the microarray dataset GSE20347, and CIT expression in ESCC cell l...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292831/ https://www.ncbi.nlm.nih.gov/pubmed/34305997 http://dx.doi.org/10.3389/fgene.2021.628547 |
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author | Lu, Wenfeng Dong, Yun Cui, Qing Wang, Yuhan Yang, Xiwen Cai, Xiaoyue Zhang, Ming |
author_facet | Lu, Wenfeng Dong, Yun Cui, Qing Wang, Yuhan Yang, Xiwen Cai, Xiaoyue Zhang, Ming |
author_sort | Lu, Wenfeng |
collection | PubMed |
description | OBJECTIVE: This study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC). METHODS: Citron 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. RESULTS: Citron 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. CONCLUSION: Our 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. |
format | Online Article Text |
id | pubmed-8292831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82928312021-07-22 High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma Lu, Wenfeng Dong, Yun Cui, Qing Wang, Yuhan Yang, Xiwen Cai, Xiaoyue Zhang, Ming Front Genet Genetics OBJECTIVE: This study aimed to investigate the role and potential regulatory mechanism of citron kinase (CIT) in esophageal squamous cell carcinoma (ESCC). METHODS: Citron 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. RESULTS: Citron 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. CONCLUSION: Our 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. Frontiers Media S.A. 2021-07-07 /pmc/articles/PMC8292831/ /pubmed/34305997 http://dx.doi.org/10.3389/fgene.2021.628547 Text en Copyright © 2021 Lu, Dong, Cui, Wang, Yang, Cai and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Lu, Wenfeng Dong, Yun Cui, Qing Wang, Yuhan Yang, Xiwen Cai, Xiaoyue Zhang, Ming High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma |
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 | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292831/ https://www.ncbi.nlm.nih.gov/pubmed/34305997 http://dx.doi.org/10.3389/fgene.2021.628547 |
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