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Revealing the Roles of the SH3GLB1-Hydrogen Peroxide Axis in Glioblastoma Multiforme Cells
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作者 Wei-Ting Hsueh Kwang-Yu Chang +8 位作者 Chin-Chuan Tsai Kuan-Tso Chen Kuen-Jang Tsai Zi-Xuan Hong Chan-Chuan Liu Jui-Mei Chu Li-Ying Qiu Yu-Yan Lan Chia-Hung Chien 《Oncology Research》 2026年第2期379-401,共23页
Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),wh... Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2)to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2)redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2)signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2)reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2)signaling.GBM cells were used to verify the role of H_(2)O_(2)signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2)via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2)levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance. 展开更多
关键词 sh3 domain GRB2-like endophilin B1 GLIOBLASTOMA H_(2)O_(2) redox MITOCHONDRIA
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SH3BGRL对胃癌细胞增殖、迁移的影响 被引量:2
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作者 颜海清 赖沁巧 +4 位作者 吴留成 王婷安 夏想 黄名威 覃宇周 《中国癌症防治杂志》 CAS 2024年第3期285-294,共10页
目的探讨SH3结构域结合富含谷氨酸的蛋白质(SH3 binding glutamic acid-rich protein like,SH3BGRL)对胃癌细胞增殖、迁移能力的影响及其作用机制。方法基于TCGA、GTEx及GEO数据库,通过生物信息学分析SH3BGRL在胃癌组织及正常胃黏膜上... 目的探讨SH3结构域结合富含谷氨酸的蛋白质(SH3 binding glutamic acid-rich protein like,SH3BGRL)对胃癌细胞增殖、迁移能力的影响及其作用机制。方法基于TCGA、GTEx及GEO数据库,通过生物信息学分析SH3BGRL在胃癌组织及正常胃黏膜上皮组织中的表达情况;通过HPA数据库获取SH3BGRL蛋白在胃癌组织及正常胃黏膜上皮组织中的表达图谱;并基于TCGA数据库的SH3BGRL表达水平进行高、低表达分组,分析其对胃癌患者预后、免疫细胞浸润和免疫治疗的影响。通过临床标本IHC染色观察SH3BGRL蛋白在胃癌中的表达情况;采用RT-qPCR检测SH3BGRL在胃癌细胞系和正常胃黏膜上皮细胞GES-1中的表达水平。将胃癌HGC-27及NCI-N87细胞进行siRNA转染分为si-NC组(转染阴性对照组)、si-SH3BGRL组(沉默SH3BGRL组),并通过RT-qPCR及Western blot验证是否转染成功。采用CCK-8及Transwell实验检测细胞增殖和迁移能力,随后诱导THP-1单核细胞分化为M0巨噬细胞,并将分化后的M0巨噬细胞和转染后的胃癌细胞进行共培养,采用RT-qPCR及细胞免疫荧光检测共培养之后M2巨噬细胞标志物的改变,并采用RT-qPCR检测SH3BGRL沉默胃癌细胞中CSF1的表达水平。结果生物信息学分析结果显示,与正常胃黏膜上皮组织相比,SH3BGRL在胃癌组织中表达上调(均P<0.01),且SH3BGRL高表达者总生存期和无进展生存期比SH3BGRL低表达的患者短(均P<0.01)。SH3BGRL高表达者M2巨噬细胞浸润比例更高,与免疫治疗低应答率相关(均P<0.01)。IHC染色结果表明,SH3BGRL蛋白在胃癌组织中表达上调(P<0.001)。与GES-1细胞相比,SH3BGRL在胃癌HGC-27及NCI-N87细胞中的mRNA表达水平均显著上调(均P<0.01)。与si-NC组相比,沉默SH3BGRL后HGC-27和NCI-N87细胞的增殖能力明显下降(均P<0.01),HGC-27细胞迁移能力显著下降(P<0.01)。M0巨噬细胞与沉默SH3BGRL的HGC-27及NCI-N87共培养后,M2巨噬细胞标志物CD163、CD206及Arg1均下调(均P<0.01)。在HGC-27及NCIN87细胞中沉默SH3BGRL后,NF-κB信号通路的靶基因CSF1显著下调(均P<0.01)。结论SH3BGRL在胃癌中表达上调,沉默SH3BGRL能抑制胃癌细胞增殖和迁移,其机制可能与抑制M2巨噬细胞极化进而形成免疫抑制肿瘤微环境有关。 展开更多
关键词 胃癌 sh3结构域结合富含谷氨酸的蛋白质 增殖 迁移 肿瘤微环境 M2巨噬细胞极化
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SH3结构域谷氨酸富集样蛋白3在非小细胞肺癌中的表达及意义 被引量:1
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作者 王巍伟 王珊珊 张曼 《肿瘤学杂志》 CAS 2020年第7期582-585,共4页
[目的]评价SH3结构域谷氨酸富集样蛋白3(SH3BGRL3)在非小细胞肺癌中的表达及其与临床病理特征的相关性。[方法]选取2014年10月至2017年12月确诊并接受手术治疗的46例非小细胞肺癌患者的癌组织标本以及距离癌组织5cm以上的癌旁组织,免疫... [目的]评价SH3结构域谷氨酸富集样蛋白3(SH3BGRL3)在非小细胞肺癌中的表达及其与临床病理特征的相关性。[方法]选取2014年10月至2017年12月确诊并接受手术治疗的46例非小细胞肺癌患者的癌组织标本以及距离癌组织5cm以上的癌旁组织,免疫组化染色检测SH3BGRL3相对表达量,荧光定量RT-PCR检测SH3BGRL3 m RNA表达。[结果]癌组织中SH3BGRL3相对表达量、SH3BGRL3 mRNA表达高于癌旁组织(P<0.05)。肿瘤体积≥5cm3、侵及浆膜、病理分期Ⅲ~Ⅳ期、有淋巴结转移患者SH3BGRL3、SH3BGRL3 m RNA相对表达量高于肿瘤体积<5cm3、未及浆膜、病理分期Ⅰ~Ⅱ期、无淋巴结转移患者(P<0.05)。病理分期、SH3BGRL3、SH3BGRL3 mRNA表达是影响非小细胞肺癌患者预后的主要危险因素。[结论]SH3BGRL3在非小细胞肺癌中呈现异常高表达,且与肿瘤体积、浸润程度、病理分期、淋巴结转移等临床病理参数具有一定相关性。SH3BGRL3、SH3BGRL3 m RNA表达是影响非小细胞肺癌患者预后的危险因素。 展开更多
关键词 sh3结构域谷氨酸富集样蛋白3 非小细胞肺癌 淋巴结转移
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Flocculation and modification of sweet potato starch using sour-liquid fermentation:Effect of individual bacteria strains
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作者 Xi Zhang Yi Li +4 位作者 Yang Gu Yuan Wang Pamela Owusu Osei Xiaomeng Wu Xiaojun Liao 《Food Bioscience》 2025年第3期1212-1223,共12页
Sour liquid fermentation is a traditional and unique method used in China to produce starch that has favorable sensory evaluation,especially a pleasant mouthfeel.However,the complexity of the natural microbial flora u... Sour liquid fermentation is a traditional and unique method used in China to produce starch that has favorable sensory evaluation,especially a pleasant mouthfeel.However,the complexity of the natural microbial flora used in the method often caused severe fluctuations in production efficiency and product quality.Hence,it is important to explore the performance and impact of each starch-flocculating bacteria on starch structure.In this study,five previously isolated starch-flocculating bacterial strains were used to ferment sweet potato starch individually.Through analyzing fermentation parameters,Leuconostoc citreum SJ-48 was identified as the strain with the highest starch flocculation ability.A more dispersed particle size distribution of starch after fermentation was observed,possibly due to the clumping of starch granules by the bacteria.It was found that the amylose content of fermented starch increased by 27.57%-42.28%,and the relative crystallinity of starch increased significantly after fermentation.Finally,the starch-binding proteins of the bacterial cell were characterized using LC-ESI-MS/MS,and it was revealed that the strong starch flocculation ability of L.citreum SJ-48 was linked to the glycoside hydrolase family 70 on its surface.This study demonstrated that the discrepancies in the flocculation ability of the different bacterial strains and subsequent changes in the fermented starch properties were mainly influenced by the different proteins on their surfaces. 展开更多
关键词 Sour liquid method Starch-flocculating bacterial cells Starch modification Starch-binding proteins sh3-like domain-containing protein
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