Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Shanghai Key Clinical Disciplines of Otorhinolaryngology, Shanghai, PR China.
BMC Cancer. 2023 Oct 17;23(1):990. doi: 10.1186/s12885-023-11439-4.
To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC).
The prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins.
Fn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH, which could be proven by HO assay and N-acetylcysteine.
Higher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.
研究产黑色素普雷沃菌（Fn）如何促进氧化应激，并介导下咽鳞癌（HPSCC）中的增殖和自噬。
回顾性分析 82 例 HPSCC 病例的预后。Fn 与 HPSCC 细胞系 FaDu 共培养。观察到 DNA 损伤反应后，进行 NUDT1 的敲低（shNUDT1 组）。CCK8 和肿瘤发生测定用于增殖观察，线粒体 ROS（MitoROS）测量用于检测细胞内氧化应激，ELISA 用于分析细胞中 8-氧-2'-脱氧鸟苷（8-oxo-dG）的浓度。双荧光素酶报告实验阐明了 miR-361-3p 与 NUDT1 的联系。用电子显微镜观察自噬流并分析相关蛋白。
Fn 与 NUDT1 高度相关。体内和体外，shNUDT1 组的增殖均低于正常 FaDu（NC 组）。shNUDT1 组的 8-oxo-dG 和 γH2AX 升高。与 Fn 组相比，shNUDT1Fn 组细胞内 ROS 减少。上调 miR-361-3p 可抑制 NUDT1 的表达及其下游的增殖和自噬。Fn 通过 OH 调节 miR-361-3p，HO 测定和 N-乙酰半胱氨酸可证明这一点。
HPSCC 患者中较高的 Fn 提示预后较差。NUDT1 可能影响细胞增殖和自噬，并调节 DNA 损伤反应。微生物组-癌症研究中首次引入了氧化应激诱导的 miR-361-3p/NUDT1 轴。
