肝癌,特别是肝细胞癌(HCC),对人类生命构成重大的全球威胁。推动创新诊断和治疗方法的发展,检查HCC的隐藏特征是至关重要的,特别是它的3D基因组结构,这一点还没有得到很好的理解。在这项研究中,我们调查了四种肝癌细胞系Hep3B的3D基因组组织,Huh1,Huh7和SNU449-使用原位Hi-C并测定转座酶可接近的染色质测序。我们的研究结果表明,肝癌细胞系有更多的长期相互作用,染色体内和染色体间,与人类乳腺上皮细胞(HMEC)相比。出乎意料的是,HCC细胞系在megabase(Mb)规模上显示细胞系特异性区室修饰,这可能被用来确定HCC亚型。在亚Mb级,与HMEC相比,我们观察到HCC细胞系中TAD(拓扑相关域)内相互作用和染色质环的减少。最后,我们发现了基因表达与SLC8A1的3D染色质结构之间的相关性,SLC8A1编码一种钠钙反转运蛋白,通过比较HCC细胞系和HMEC,已知其调节可诱导细胞凋亡。我们的发现表明,肝癌细胞系有一个独特的3D基因组组织,不同于正常和其他癌细胞的基于区室的分析,TAD,和染色质循环。总的来说,我们以此为证据,证明基因组组织在癌症表型确定中起着至关重要的作用。进一步探索肝癌的表观遗传学将有助于我们更好地理解特定的基因调控机制,并发现癌症治疗的新靶点。
Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines-Hep3B, Huh1, Huh7, and SNU449-using in situ Hi-C and assay for transposase-accessible chromatin sequencing. Our findings revealed that HCC cell lines had more long-range interactions, both intra-and interchromosomal, compared to human mammary epithelial cells (HMECs). Unexpectedly, HCC cell lines displayed cell line-specific compartmental modifications at the megabase (Mb) scale, which could potentially be leveraged in determining HCC subtypes. At the sub-Mb scale, we observed decreases in intra-TAD (topologically associated domain) interactions and chromatin loops in HCC cell lines compared to HMECs. Lastly, we discovered a correlation between gene expression and the 3D chromatin architecture of SLC8A1, which encodes a sodium-calcium antiporter whose modulation is known to induce apoptosis by comparison between HCC cell lines and HMECs. Our findings suggest that HCC cell lines have a distinct 3D genome organization that is different from those of normal and other cancer cells based on the analysis of compartments, TADs, and chromatin loops. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will help us to better understand specific gene regulation mechanisms and uncover novel targets for cancer treatment.