Table_3_Proteomic Characterization of Proliferation Inhibition of Well-Differentiated Laryngeal Squamous Cell Carcinoma Cells Under Below-Background Radiation in a Deep Underground Environment.XLSX

Background: There has been a considerable concern about cancer induction in response to radiation exposure. However, only a limited number of studies have focused on the biological effects of below-background radiation (BBR) in deep underground environments. To improve our understanding of the effects of BBR on cancer, we studied its biological impact on well-differentiated laryngeal squamous cell carcinoma cells (FD-LSC-1) in a deep underground laboratory (DUGL).
Methods: The growth curve, morphological, and quantitative proteomic experiments were performed on FD-LSC-1 cells cultured in the DUGL and above-ground laboratory (AGL).
Results: The proliferation of FD-LSC-1 cells from the DUGL group was delayed compared to that of cells from the AGL group. Transmission electron microscopy scans of the cells from the DUGL group indicated the presence of hypertrophic endoplasmic reticulum (ER) and a higher number of ER. At a cutoff of absolute fold change ≥ 1.2 and p < 0.05, 807 differentially abundant proteins (DAPs; 536 upregulated proteins and 271 downregulated proteins in the cells cultured in the DUGL) were detected. KEGG pathway analysis of these DAPs revealed that seven pathways were enriched. These included ribosome (p < 0.0001), spliceosome (p = 0.0001), oxidative phosphorylation (p = 0.0001), protein export (p = 0.0001), thermogenesis (p = 0.0003), protein processing in the endoplasmic reticulum (p = 0.0108), and non-alcoholic fatty liver disease (p = 0.0421).
Conclusion: The BBR environment inhibited the proliferation of FD-LSC-1 cells. Additionally, it induced changes in protein expression associated with the ribosome, gene spliceosome, RNA transport, and energy metabolism among others. The changes in protein expression might form the molecular basis for proliferation inhibition and enhanced survivability of cells adapting to BBR exposure in a deep underground environment. RPL26, RPS27, ZMAT2, PRPF40A, SNRPD2, SLU7, SRSF5, SRSF3, SNRPF, WFS1, STT3B, CANX, ERP29, HSPA5, COX6B1, UQCRH, and ATP6V1G1 were the core proteins associated with the BBR stress response in cells.

研究背景：辐射暴露诱发癌症的问题已受到广泛关注。然而，针对深层地下环境中低于本底辐射（below-background radiation, BBR）的生物学效应的研究却较为有限。为加深我们对低于本底辐射致癌效应的理解，本研究于地下深部实验室（deep underground laboratory, DUGL）中，探究了其对高分化喉鳞状细胞癌细胞（FD-LSC-1）的生物学影响。
研究方法：本研究对分别培养于地下深部实验室及地面实验室（above-ground laboratory, AGL）的FD-LSC-1细胞开展了生长曲线、形态学及定量蛋白质组学实验。
研究结果：与地面实验室组细胞相比，地下深部实验室组FD-LSC-1细胞的增殖速率显著延迟。透射电子显微镜观察显示，地下深部实验室组细胞存在内质网（endoplasmic reticulum, ER）肥大且内质网数量增多。以绝对倍数变化≥1.2且p<0.05为筛选阈值，共检测到807个差异丰度蛋白（differentially abundant proteins, DAPs），其中地下深部实验室培养的细胞内有536个蛋白上调、271个蛋白下调。对上述差异丰度蛋白的KEGG通路富集分析显示，7条通路发生显著富集，分别为核糖体（p<0.0001）、剪接体（p=0.0001）、氧化磷酸化（p=0.0001）、蛋白质输出（p=0.0001）、产热（p=0.0003）、内质网内蛋白质加工（p=0.0108）以及非酒精性脂肪肝（p=0.0421）。
研究结论：低于本底辐射环境可抑制FD-LSC-1细胞的增殖，并诱导核糖体、基因剪接体、RNA转运及能量代谢等相关蛋白质表达谱发生改变。此类蛋白质表达变化或可构成细胞增殖受抑，以及适应深层地下低于本底辐射环境后存活率提升的分子基础。RPL26、RPS27、ZMAT2、PRPF40A、SNRPD2、SLU7、SRSF5、SRSF3、SNRPF、WFS1、STT3B、CANX、ERP29、HSPA5、COX6B1、UQCRH及ATP6V1G1是细胞应对低于本底辐射胁迫反应的核心蛋白。