表观基因组分析揭示出结直肠癌转移能力循环肿瘤细胞的独特DNA甲基化程序。
Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer.
发表日期:2023 Sep 16
作者:
Aida Bao-Caamano, Nicolás Costa-Fraga, Laure Cayrefourcq, María Amalia Jácome, Aitor Rodriguez-Casanova, Laura Muinelo-Romay, Rafael López-López, Catherine Alix-Panabières, Angel Díaz-Lagares
来源:
Epigenetics & Chromatin
摘要:
循环肿瘤细胞(CTCs)和表观遗传变化参与了从实体肿瘤的转移,如结直肠癌(CRC)。本研究旨在表征CRC转移能力的CTCs的DNA甲基化谱。分析了人类CRC细胞系CTC-MCC-41的DNA甲基组,并与原发性(HT29,Caco2,HCT116,RKO)和转移性(SW620和COLO205)CRC细胞进行了比较。还评估了CTC-MCC-41的甲基化与转录谱的关联。差异甲基化的CpGs使用pyrosequencing和qMSP进行了验证。与原发性和转移性CRC细胞相比,CTC-MCC-41的甲基化谱总体上存在差异,并以富集在CpG贫区域的轻度低甲基化CpGs为主要特征。CTC-MCC-41的启动子CpG岛和滨区显示出独特的甲基化谱,与转录程序和相关的癌症途径(主要是Wnt信号通路)相关联。验证了CTC-MCC-41中相关基因的表观遗传调控。这项研究为转移能力的CTCs的表观基因组景观提供了新的洞察,揭示了转移发展的生物学信息,以及CRC患者的新潜在生物标志物和治疗靶点。©2023. Springer Nature Limited.
Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis from solid tumors, such as colorectal cancer (CRC). The aim of this study was to characterize the DNA methylation profile of metastasis-competent CTCs in CRC. The DNA methylome of the human CRC-derived cell line CTC-MCC-41 was analyzed and compared with primary (HT29, Caco2, HCT116, RKO) and metastatic (SW620 and COLO205) CRC cells. The association between methylation and the transcriptional profile of CTC-MCC-41 was also evaluated. Differentially methylated CpGs were validated with pyrosequencing and qMSP. Compared to primary and metastatic CRC cells, the methylation profile of CTC-MCC-41 was globally different and characterized by a slight predominance of hypomethylated CpGs mainly distributed in CpG-poor regions. Promoter CpG islands and shore regions of CTC-MCC-41 displayed a unique methylation profile that was associated with the transcriptional program and relevant cancer pathways, mainly Wnt signaling. The epigenetic regulation of relevant genes in CTC-MCC-41 was validated. This study provides new insights into the epigenomic landscape of metastasis-competent CTCs, revealing biological information for metastasis development, as well as new potential biomarkers and therapeutic targets for CRC patients.© 2023. Springer Nature Limited.