最近的研究表明，NDUFS1在人类肿瘤中具有重要作用；然而，NDUFS1对胃癌（GC）的影响仍不完全清楚。我们通过免疫组织化学的西方印迹和生物信息学分析证实了NDUFS1在GC细胞中的下调。通过CCK-8、集落形成、透明层小鼠和活体内胃癌的移植实验，研究了NDUFS1对GC的影响。我们通过共聚焦反射显微镜观察了NDUFS1的表达和亚细胞定位以及线粒体反应性氧化物（mROS）的含量。结果显示GC组织和细胞系中存在NDUFS1表达的减少。此外，NDUFS1的过表达抑制了GC细胞在体外的增殖、迁移和浸润，以及在体内的生长和转移。机械上，NDUFS1的减少导致mROS-缺氧诱导因子1α（HIF1α）信号通路的激活。我们进一步明确，NDUFS1的减少通过激活mROS-HIF1α信号通路在GC细胞中上调了HIF1α的转录靶标纤维蛋白5（FBLN5）的表达。本研究结果表明，NDUFS1的下调通过激活mROS-HIF1α-FBLN5信号通路促进了GC的进展。© 2023年。作者（们）

Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood.We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy.Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells.The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.© 2023. The Author(s).