GLIS3在多种癌症中高度表达，但其在胃腺癌（GAC）中尚未得到研究。基于生物信息学分析，我们对GLIS3在GAC中的预后意义进行了分析。我们转染了GAC细胞，分别使用小干扰RNA（si-GLIS3）和GLIS3过表达质粒，并使用SB505124（转化生长因子β受体1（TGFβR1）抑制剂）和dorsomorphin（骨形成蛋白受体1（BMPR1）抑制剂）进行处理。我们使用定量逆转录聚合酶链反应（qRT-PCR）检测了GLIS3的表达。通过细胞功能分析，我们测量了GLIS3对GAC细胞增殖、浸润和迁移的影响。我们使用免疫荧光法检测了磷酸化Smad1/5（p-Smad1/5）的活化情况。我们使用免疫印迹法测定了转化生长因子β（TGF-β）1/Smad1/5信号通路相关蛋白（TGF-β1、p-Smad1、Smad1、p-Smad5、Smad5）的水平。GLIS3在GAC组织和细胞系中高水平表达，并且其高表达可能预示着GAC患者的不良预后。GLIS3抑制降低了GAC细胞的增殖、浸润和迁移能力，同时降低了TGF-β1的表达和Smad1/5的磷酸化水平。GLIS3过表达促进了GAC细胞的增殖、迁移、浸润、TGF-β1表达和Smad1/5的磷酸化，而SB505124能够逆转GLIS3过表达对增殖、迁移、浸润和Smad1/5磷酸化的影响，而dorsomorphin对GLIS3诱导的效应没有影响。GLIS3通过调节TGF-β1/TGFβR1/Smad1/5信号通路促进了GAC细胞的恶性表型，这可能是GAC的一种新的预后指标，并提供了GAC治疗的靶点。版权所有 © 2023 Elsevier Ltd. 保留所有权利。

GLIS3 is highly expressed in multiple cancers, but it has not been studied in gastric adenocarcinoma (GAC). Based on bioinformatics analysis, the prognostic significance of GLIS3 in GAC was analyzed. GAC cells were transfected with small interfering (si)-GLIS3 and GLIS3 overexpression plasmid as well as treated with SB505124 [an inhibitor for transforming growth factor beta receptor 1 (TGFβR1)] and dorsomorphin [an inhibitor for bone morphogenetic protein receptor 1 (BMPR1)]. The GLIS3 expression was detected using qRT-PCR. The impacts of GLIS3 on the proliferation, invasion and migration of GAC cells were measured using cell function assays. The activation of phosphor (p)-Smad1/5 was tested by immunofluorescence. Western blot was utilized to measure the level of transforming growth factor (TGF)-β1/Smad1/5 signaling pathway-related proteins (TGF-β1, p-Smad1, Smad1, p-Smad5, Smad5). GLIS3 was expressed at high levels in GAC tissues and cell lines and its high expression could indicate the poor prognosis of GAC patients. GLIS3 inhibition declined the proliferative, invasive and migratory capabilities as well as TGF-β1 expression and phosphorylation of Smad1/5 in GAC cells. Overexpressed GLIS3 promoted proliferation, migration, invasion, TGF-β1 expression and Smad1/5 phosphorylation in GAC cells, with SB505124 reversing the effects of overexpressed GLIS3 on proliferation, migration, invasion and Smad1/5 phosphorylation whereas dorsomorphin exhibiting no influence on GLIS3-induced effects. GLIS3 facilitated the malignant phenotype of GAC cells via regulating TGF-β1/TGFβR1/Smad1/5 pathway, which may be a novel prognostic indicator of GAC and provided a target for GAC treatment.Copyright © 2023 Elsevier Ltd. All rights reserved.