Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent
Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent
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羟基类固醇磺基转移酶 2B1 影响胃上皮功能和致癌剂诱导的致癌作用
DOI：
10.1186/s12944-019-1149-6
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发表时间：
2019-11-22
影响因子：
4.5
通讯作者：
Li, Xiaobo
中科院分区：
文献类型：
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作者：
Hong, Wenting;Guo, Fenghua;Li, Xiaobo
背景健康的胃粘膜上皮具有肿瘤抑制作用。胃上皮细胞功能障碍与胃癌的发生发展密切相关。在胃上皮细胞中大量存在的羟类固醇硫转移酶2B1(SULT2B1)可进一步使胃上皮细胞中由食物或胆固醇氧化提供的氧化甾醇进一步硫化。然而，SULT2B1对胃上皮细胞功能和胃癌发生的影响尚不清楚。方法用致癌剂3-甲基胆蒽(3-MCA)建立小鼠胃癌模型。用CRISPR/CAS9基因组编辑系统构建了SULT2B1缺失(SULT2B1−/−)人胃上皮细胞系GES-1。结果SULT2B1−/−小鼠的胃癌发病率高于野生型(WT)小鼠。在胃上皮细胞中，腺病毒介导的SULT2B1b过表达降低了24(R/S)、25-环氧胆固醇(24(R/S)、25-EC)和27-羟基胆固醇(27HC)的水平。这种情况也增加了PI3K/AKT信号，促进了胃上皮细胞的增殖、上皮化和上皮发育。而SULT2B1缺失或SULT2B1基因敲除可抑制PI3K/AKT信号通路，抑制上皮细胞上皮化，抑制创面愈合，诱导胃上皮细胞恶性转化。结论正常胃上皮中SULT2B1的高表达可能通过PI3K/AKT信号通路维持上皮功能，抑制致癌剂诱导的胃癌发生。
BackgroundA 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.MethodsA 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.ResultsThe 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.ConclusionsThe 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.