Department of Preventive Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, 1258 Fuxing Middle Road, Shanghai, 200001, China.
Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China.
J Transl Med. 2024 Nov 29;22(1):1082. doi: 10.1186/s12967-024-05885-2.
Radiotherapy sensitivity is associated with the prognosis of patients with tongue squamous cell carcinoma (TSCC). In the present study, we proposed to explore the specific mechanism of interventional radiology (IR) therapy for TSCC in vitro and in vivo. TSCC cells were treated with 6 Gy IR and tumor bearing mice were treated with 20 Gy × 1 IR. DIA quantitative proteomics along with bioinformatics analysis were conducted in TSCC cells to investigate differential proteins related to IR and relation of which involved in TMEM147 and SPHK1 was confirmed by immunoprecipitation. Cell proliferation, apoptosis, autophagy& autophagy flux along with calcium signaling pathway detection were performed in vitro and in vivo. Our results showed that IR induced increasing calcium levels accompanied by up-regulated TMEM147 and down-regulated SPHK1 along with enhancing autophagy together with apoptosis. The effect of calcium overloading induced by IR on autophagy and apoptosis was dependent on increasing TMEM147 and decreasing SPHK1. However, IR-induced autophagy and apoptosis tended to be independent of only increasing calcium levels when down-regulating TMEM147 or up-regulating SPHK1 expression in vitro and in vivo. Our study suggested that calcium-mediated TMEM147/SPHK1 may promote autophagy and apoptosis to improve radiotherapy sensitivity in TSCC.
放射敏感性与舌鳞状细胞癌（TSCC）患者的预后相关。在本研究中，我们拟在体外和体内探索介入放射学（IR）治疗 TSCC 的具体机制。用 6GyIR 处理 TSCC 细胞，用 20Gy×1IR 处理荷瘤小鼠。在 TSCC 细胞中进行 DIA 定量蛋白质组学和生物信息学分析，以研究与 IR 相关的差异蛋白，并通过免疫沉淀证实了其涉及 TMEM147 和 SPHK1 的关系。在体外和体内进行细胞增殖、凋亡、自噬和自噬流以及钙信号通路检测。结果表明，IR 诱导钙水平升高，同时上调 TMEM147，下调 SPHK1，增强自噬并促进凋亡。IR 诱导的自噬和凋亡对钙超载的作用依赖于增加 TMEM147 和减少 SPHK1。然而，当体外和体内下调 TMEM147 或上调 SPHK1 表达时，IR 诱导的自噬和凋亡倾向于不依赖于仅增加钙水平。本研究表明，钙介导的 TMEM147/SPHK1 可能通过促进自噬和凋亡来提高 TSCC 的放射敏感性。
