Hydroxysteroid sulfotransferase 2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent

Abstract

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.

Obesity and Cancer: 27-Hydroxycholesterol, the Missing Link

“…In addition, hydroxysteroid sulfotransferase decreases the levels of cholesterol and oxysterols including 27HC [ 95 , 96 ]. Although the expression and function of this enzyme are related to some cancers including skin, liver, and gastric cancers [ 96 , 97 ], the enzyme is not specific to 27HC and its physiological function is not yet clear. In regard to pharmacological interventions of 27HC levels, statins, cholesterol-lowering drugs, and some CYP enzyme inhibitors reduce the 27HC levels as well, but they are not specific to 27HC, so it is hard to examine the direct impact of decreased 27HC on the disease [ 72 ].…”

Cholesterol sulfate alleviates ulcerative colitis by promoting cholesterol biosynthesis in colonic epithelial cells

“…Cholesterol sulfate (CS) is a sulfated derivative of cholesterol catalyzed by hydroxysteroid sulfotransferase 2B1 (SULT2B1) 12 , 13 . Our previous study, in addition to others, found that SULT2B1 promoted liver regeneration in a partial hepatectomy (PH) model, increased hepatic oval cell proliferation in a chemical-induced liver injury model, and accelerated the growth of multiple cells 14 – 17 . CS is critical in several biological processes, including epidermal differentiation, sperm capacitation, platelet adhesion, blood clotting, fibrinolysis, gluconeogenesis, T cell receptor signaling, and cell invasion 18 – 22 .…”

Characterization of the mechanism of Scutellaria baicalensis on reversing radio-resistance in colorectal cancer

“…Hong et al. [47] showed that SULT2B1 affects gastric epithelial function and carcinogenesis induced by a carcinogenic agent. Hu et al.…”