KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression
Abstract KDM6B (Lysine-specific demethylase 6B) is a histone lysine demethyltransferase that plays a key role in many types of cancers. However, its potential role in gastric cancer (GC) remains unclear. Here, we focused on the clinical significance and potential role of KDM6B in GC. We found that t...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05458-5 |
| _version_ | 1797977223757561856 |
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| author | Fen Liu Yue Wang Zongcheng Yang Xiujie Cui Lixin Zheng Yue Fu Wei Shao Lu Zhang Qing Yang Jihui Jia |
| author_facet | Fen Liu Yue Wang Zongcheng Yang Xiujie Cui Lixin Zheng Yue Fu Wei Shao Lu Zhang Qing Yang Jihui Jia |
| author_sort | Fen Liu |
| collection | DOAJ |
| description | Abstract KDM6B (Lysine-specific demethylase 6B) is a histone lysine demethyltransferase that plays a key role in many types of cancers. However, its potential role in gastric cancer (GC) remains unclear. Here, we focused on the clinical significance and potential role of KDM6B in GC. We found that the KDM6B expression is upregulated in GC tissues and that its high expression in patients is related to poor prognosis. KDM6B ectopic expression promotes GC cells’ proliferation and metastasis, while its inhibition has opposite effects in vitro and in vivo. Mechanistically, KDM6B promotes GC cells proliferation and metastasis through its enzymatic activity through the induction of H3K27me3 demethylation near the CXCR4 (C-X-C chemokine receptor type 4) promoter region, resulting in the upregulation of CXCR4 expression. Furthermore, H. pylori was found to induce KDM6B expression. In conclusion, our results suggest that KDM6B is aberrantly expressed in GC and plays a key role in gastric carcinogenesis and metastasis through CXCR4 upregulation. Our work also suggests that KDM6B may be a potential oncogenic factor and a therapeutic target for GC. |
| first_indexed | 2024-04-11T05:04:38Z |
| format | Article |
| id | doaj.art-d31fbb3d45ae4988b5d27d93f9682797 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T05:04:38Z |
| publishDate | 2022-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-d31fbb3d45ae4988b5d27d93f96827972022-12-25T12:31:55ZengNature Publishing GroupCell Death and Disease2041-48892022-12-01131211310.1038/s41419-022-05458-5KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expressionFen Liu0Yue Wang1Zongcheng Yang2Xiujie Cui3Lixin Zheng4Yue Fu5Wei Shao6Lu Zhang7Qing Yang8Jihui Jia9Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong UniversityDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong UniversityDepartment of stomatology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Pathology, The Second Hospital, Shandong UniversityDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong UniversityDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong UniversityDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Cheeloo College of Medicine, Shandong UniversityDepartment of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong UniversityAbstract KDM6B (Lysine-specific demethylase 6B) is a histone lysine demethyltransferase that plays a key role in many types of cancers. However, its potential role in gastric cancer (GC) remains unclear. Here, we focused on the clinical significance and potential role of KDM6B in GC. We found that the KDM6B expression is upregulated in GC tissues and that its high expression in patients is related to poor prognosis. KDM6B ectopic expression promotes GC cells’ proliferation and metastasis, while its inhibition has opposite effects in vitro and in vivo. Mechanistically, KDM6B promotes GC cells proliferation and metastasis through its enzymatic activity through the induction of H3K27me3 demethylation near the CXCR4 (C-X-C chemokine receptor type 4) promoter region, resulting in the upregulation of CXCR4 expression. Furthermore, H. pylori was found to induce KDM6B expression. In conclusion, our results suggest that KDM6B is aberrantly expressed in GC and plays a key role in gastric carcinogenesis and metastasis through CXCR4 upregulation. Our work also suggests that KDM6B may be a potential oncogenic factor and a therapeutic target for GC.https://doi.org/10.1038/s41419-022-05458-5 |
| spellingShingle | Fen Liu Yue Wang Zongcheng Yang Xiujie Cui Lixin Zheng Yue Fu Wei Shao Lu Zhang Qing Yang Jihui Jia KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression Cell Death and Disease |
| title | KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression |
| title_full | KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression |
| title_fullStr | KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression |
| title_full_unstemmed | KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression |
| title_short | KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression |
| title_sort | kdm6b promotes gastric carcinogenesis and metastasis via upregulation of cxcr4 expression |
| url | https://doi.org/10.1038/s41419-022-05458-5 |
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