Nucleosome assembly during DNA replication is dependent on histone chaperones. Recent studies suggest that dysregulated histone chaperones contribute to cancer progression, including gastric cancer (GC). Further studies are required to explore the prognostic and therapeutic implications of histone chaperones and their mechanisms of action in GC progression. Here we identified histone chaperone ASF1B as a potential biomarker for GC proliferation and prognosis. ASF1B was significantly upregulated in GC, which was associated with poor prognosis. and experiments demonstrated that the inhibition of ASF1B suppressed the malignant characteristics of GC, while overexpression of ASF1B had the opposite effect. Mechanistically, transcription factor FOXM1 directly bound to the -promoter region, thereby regulating its transcription. Treatment with thiostrepton, a FOXM1 inhibitor, not only suppressed ASF1B expression, but also inhibited GC progression. Furthermore, ASF1B regulated the mitochondrial protein peroxiredoxin 3 (PRDX3) transcription in a FOXM1-dependent manner. The crucial role of ASF1B-regulated PRDX3 in GC cell proliferation and oxidative stress balance was also elucidated. In summary, our study suggests that the FOXM1-ASF1B-PRDX3 axis is a potential therapeutic target for treating GC.

中文翻译：

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FOXM1/ASF1B/PRDX3轴的激活赋予胃癌过度增殖和抗氧化应激反应性

DNA 复制期间的核小体组装依赖于组蛋白伴侣。最近的研究表明，失调的组蛋白伴侣会导致癌症进展，包括胃癌 (GC)。需要进一步的研究来探索组蛋白伴侣的预后和治疗意义及其在 GC 进展中的作用机制。在这里，我们将组蛋白伴侣 ASF1B 确定为 GC 增殖和预后的潜在生物标志物。 ASF1B 在 GC 中显着上调，这与不良预后相关。实验证明，抑制ASF1B可以抑制GC的恶性特征，而过表达ASF1B则具有相反的效果。从机制上讲，转录因子FOXM1直接与β启动子区域结合，从而调节其转录。使用 FOXM1 抑制剂硫链丝菌肽治疗不仅可以抑制 ASF1B 表达，还可以抑制 GC 进展。此外，ASF1B 以 FOXM1 依赖性方式调节线粒体蛋白过氧化还原蛋白 3 (PRDX3) 转录。还阐明了 ASF1B 调节的 PRDX3 在 GC 细胞增殖和氧化应激平衡中的关键作用。总之，我们的研究表明 FOXM1-ASF1B-PRDX3 轴是治疗 GC 的潜在治疗靶点。