Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmain Road, Kunming, China.
Department of Cardiovascular Surgery, The First People's Hospital of Yunnan Province, Kunming, China.
BMC Med Genomics. 2022 Aug 26;15(1):185. doi: 10.1186/s12920-022-01338-1.
Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor, which poses a serious threat to human health. Histone 3 lysine 9 trimethylation (H3K9me3) is a post-translational modification involved in regulating a broad range of biological processes and has been considered as potential therapeutic target in types of cancer. However, there is limited research on investigating profiles of histone modification H3K9me3 in ICC patients.
In this study, we applied the ChIP-seq technique to investigate the effect of H3K9me3 on ICC. Anti-H3K9me3 antibody was used for ChIP-seq in ICC (RBE cell lines) and HIBEpic (normal cell lines). MACS2 (peak-calling tools) was then used to identify the peaks recorded in RBE and HIBEpic cell lines. Gene expression, mutation and clinical data were downloaded from TCGA and cBioPortal databases.
H3K9me3 exhibited abnormal methylation and influenced the process of abnormal gene expression in patients suffering from ICC. The Wnt/β-Catenin signaling pathway (also known as simply the WNT signaling pathway) was enriched in H3K9me3-regulated genes.
We are the first to report that H3K9me3 may play an important role in the progression of ICC. It promotes the understanding of epigenetic molecular mechanisms for ICC.
肝内胆管癌（ICC）是一种恶性肿瘤，严重威胁人类健康。组蛋白 3 赖氨酸 9 三甲基化（H3K9me3）是一种参与调节广泛生物过程的翻译后修饰，已被认为是多种癌症的潜在治疗靶点。然而，关于 ICC 患者组蛋白修饰 H3K9me3 谱的研究有限。
在这项研究中，我们应用 ChIP-seq 技术研究了 H3K9me3 对 ICC 的影响。用抗 H3K9me3 抗体对 ICC（RBE 细胞系）和 HIBEpic（正常细胞系）进行 ChIP-seq。然后使用 MACS2（峰调用工具）来识别 RBE 和 HIBEpic 细胞系中记录的峰。从 TCGA 和 cBioPortal 数据库下载基因表达、突变和临床数据。
H3K9me3 表现出异常甲基化，影响 ICC 患者异常基因表达的过程。Wnt/β-连环蛋白信号通路（也称为 WNT 信号通路）在 H3K9me3 调控基因中富集。
我们首次报道 H3K9me3 可能在 ICC 的进展中发挥重要作用。它促进了对 ICC 中表观遗传分子机制的理解。
