Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent
Abstract Background A healthy gastric mucosal epithelium exhibits tumor-suppressive properties. Gastric epithelial cell dysfunction contributes to gastric cancer development. Oxysterols provided from food or cholesterol oxidation in the gastric epithelium may be further sulfated by hydroxysteroid su...
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12944-019-1149-6 |
| _version_ | 1831680608538984448 |
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| author | Wenting Hong Fenghua Guo Mingjie Yang Dongke Xu Ziyan Zhuang Baolin Niu Qianming Bai Xiaobo Li |
| author_facet | Wenting Hong Fenghua Guo Mingjie Yang Dongke Xu Ziyan Zhuang Baolin Niu Qianming Bai Xiaobo Li |
| author_sort | Wenting Hong |
| collection | DOAJ |
| description | Abstract Background A healthy gastric mucosal epithelium exhibits tumor-suppressive properties. Gastric epithelial cell dysfunction contributes to gastric cancer development. Oxysterols provided from food or cholesterol oxidation in the gastric epithelium may be further sulfated by hydroxysteroid sulfotransferase 2B1 (SULT2B1), which is highly abundant in the gastric epithelium. However, the effects of SULT2B1 on gastric epithelial function and gastric carcinogenesis are unclear. Methods A mouse gastric tumor model was established using carcinogenic agent 3-methylcholanthrene (3-MCA). A SULT2B1 deletion (SULT2B1−/−) human gastric epithelial line GES-1 was constructed by CRISPR/CAS9 genome editing system. Results The gastric tumor incidence was higher in the SULT2B1−/− mice than in the wild-type (WT) mice. In gastric epithelial cells, adenovirus-mediated SULT2B1b overexpression reduced the levels of oxysterols, such as 24(R/S),25-epoxycholesterol (24(R/S),25-EC) and 27-hydroxycholesterol (27HC). This condition also increased PI3K/AKT signaling to promote gastric epithelial cell proliferation, epithelization, and epithelial development. However, SULT2B1 deletion or SULT2B1 knockdown suppressed PI3K/AKT signaling, epithelial cell epithelization, and wound healing and induced gastric epithelial cell malignant transition upon 3-MCA induction. Conclusions The abundant SULT2B1 expression in normal gastric epithelium might maintain epithelial function via the PI3K/AKT signaling pathway and suppress gastric carcinogenesis induced by a carcinogenic agent. |
| first_indexed | 2024-12-20T05:40:53Z |
| format | Article |
| id | doaj.art-e36379455d874292863ea7fd919d1889 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-12-20T05:40:53Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-e36379455d874292863ea7fd919d18892022-12-21T19:51:27ZengBMCLipids in Health and Disease1476-511X2019-11-0118111410.1186/s12944-019-1149-6Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agentWenting Hong0Fenghua Guo1Mingjie Yang2Dongke Xu3Ziyan Zhuang4Baolin Niu5Qianming Bai6Xiaobo Li7Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan UniversityDepartment of General Surgery, Hua’shan Hospital, Fudan University Shanghai Medical CollegeDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan UniversityDepartment of Pathology, Fudan University Shanghai Cancer CentreDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan UniversityAbstract Background A healthy gastric mucosal epithelium exhibits tumor-suppressive properties. Gastric epithelial cell dysfunction contributes to gastric cancer development. Oxysterols provided from food or cholesterol oxidation in the gastric epithelium may be further sulfated by hydroxysteroid sulfotransferase 2B1 (SULT2B1), which is highly abundant in the gastric epithelium. However, the effects of SULT2B1 on gastric epithelial function and gastric carcinogenesis are unclear. Methods A mouse gastric tumor model was established using carcinogenic agent 3-methylcholanthrene (3-MCA). A SULT2B1 deletion (SULT2B1−/−) human gastric epithelial line GES-1 was constructed by CRISPR/CAS9 genome editing system. Results The gastric tumor incidence was higher in the SULT2B1−/− mice than in the wild-type (WT) mice. In gastric epithelial cells, adenovirus-mediated SULT2B1b overexpression reduced the levels of oxysterols, such as 24(R/S),25-epoxycholesterol (24(R/S),25-EC) and 27-hydroxycholesterol (27HC). This condition also increased PI3K/AKT signaling to promote gastric epithelial cell proliferation, epithelization, and epithelial development. However, SULT2B1 deletion or SULT2B1 knockdown suppressed PI3K/AKT signaling, epithelial cell epithelization, and wound healing and induced gastric epithelial cell malignant transition upon 3-MCA induction. Conclusions The abundant SULT2B1 expression in normal gastric epithelium might maintain epithelial function via the PI3K/AKT signaling pathway and suppress gastric carcinogenesis induced by a carcinogenic agent.http://link.springer.com/article/10.1186/s12944-019-1149-6Gastric epithelial cellHydroxysteroid Sulfotransferase 2B1 (SULT2B1)Gastric carcinogenesisOxysterolPI3K/AKT signaling |
| spellingShingle | Wenting Hong Fenghua Guo Mingjie Yang Dongke Xu Ziyan Zhuang Baolin Niu Qianming Bai Xiaobo Li Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent Lipids in Health and Disease Gastric epithelial cell Hydroxysteroid Sulfotransferase 2B1 (SULT2B1) Gastric carcinogenesis Oxysterol PI3K/AKT signaling |
| title | Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent |
| title_full | Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent |
| title_fullStr | Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent |
| title_full_unstemmed | Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent |
| title_short | Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent |
| title_sort | hydroxysteroid sulfotransferase 2b1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent |
| topic | Gastric epithelial cell Hydroxysteroid Sulfotransferase 2B1 (SULT2B1) Gastric carcinogenesis Oxysterol PI3K/AKT signaling |
| url | http://link.springer.com/article/10.1186/s12944-019-1149-6 |
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