综合3D基因组和表观基因组分析确定TP53RK和SYBU是HCC中干性和抗肿瘤免疫的关键调节因子
Integrative 3D genome and epigenomic analysis identifies TP53RK and SYBU as critical regulators of stemness and anti-tumor immunity in HCC.
摘要(中文译文)
三维（3D）基因组组织在调控基因表达和肿瘤细胞特性中发挥基础性作用。然而，高级染色质结构如何调控肝细胞癌（HCC）的干性仍不清楚。在此，我们描绘了高分化和低分化HCC细胞的3D染色质景观，揭示了与干性相关的A/B区室化、拓扑关联结构域（TAD）边界和增强子-启动子环的重塑。这些结构改变导致TP53RK和SYBU的差异表达，二者对HCC干性和进展发挥相反的作用。TP53RK通过增强线粒体自噬促进肿瘤干性，而SYBU通过抑制MAPK信号通路抑制干性。值得注意的是，TP53RK表达与PD-1呈正相关，联合抑制TP53RK和PD-1可显著增强抗肿瘤免疫。我们的研究结果确定了3D基因组结构是肿瘤干性的关键决定因素，并突出TP53RK作为HCC中有前景的治疗靶点。
Abstract
Three-dimensional (3D) genome organization plays a fundamental role in governing gene regulation and tumor cell properties. However, how higher-order chromatin architecture regulates stemness in hepatocellular carcinoma (HCC) remains unclear. Here, we delineated the 3D chromatin landscapes of well- and poorly differentiated HCC cells and uncovered stemness-associated rewiring of A/B compartmentalization, topologically associating domain (TAD) boundaries, and enhancer-promoter loops. These structural alterations lead to the differential expression of TP53RK and SYBU, which exert opposing effects on HCC stemness and progression. TP53RK promotes tumor stemness by enhancing mitophagy, whereas SYBU suppresses stemness by inhibiting MAPK signaling. Notably, TP53RK expression correlates positively with PD-1, and the combined inhibition of TP53RK and PD-1 markedly enhances anti-tumor immunity. Our findings identify the 3D genome architecture as a key determinant of tumor stemness and highlight TP53RK as a promising therapeutic target in HCC.
如何引用
AMA
Yanmei Yang, Peixian Li, Liangbo Zhao, Lingwei Zhang, Hong Chen, Hao Xing, et al. Integrative 3D genome and epigenomic analysis identifies TP53RK and SYBU as critical regulators of stemness and anti-tumor immunity in HCC.. Cell reports. 2026; doi:10.1016/j.celrep.2026.117797.
APA
Yanmei Yang, Peixian Li, Liangbo Zhao, Lingwei Zhang, Hong Chen, Hao Xing, et al (2026). Integrative 3D genome and epigenomic analysis identifies TP53RK and SYBU as critical regulators of stemness and anti-tumor immunity in HCC.. Cell reports. https://doi.org/10.1016/j.celrep.2026.117797
GB/T 7714
Yanmei Yang, Peixian Li, Liangbo Zhao, Lingwei Zhang, Hong Chen, Hao Xing, et al. Integrative 3D genome and epigenomic analysis identifies TP53RK and SYBU as critical regulators of stemness and anti-tumor immunity in HCC.[J]. Cell reports, 2026 doi:10.1016/j.celrep.2026.117797.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出