食管癌中癌症干细胞的全基因组 DNA 甲基化模式。
Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer.
机构信息
Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820983793. doi: 10.1177/1533033820983793.
BACKGROUND
Cancer stem cells (CSCs) are considered the main cause of cancer recurrence and metastasis, and DNA methylation is involved in the maintenance of CSCs. However, the methylation profile of esophageal CSCs remains unknown.
METHODS
Side population (SP) cells were isolated from esophageal squamous cell carcinoma (ESCC) cell lines KYSE150 and EC109. Sphere-forming cells were collected from human primary esophageal cancer cells. SP cells and sphere-forming cells were used as substitutes for cancer stem-like cells. We investigated the genome-wide DNA methylation profile in esophageal cancer stem-like cells using reduced representation bisulfite sequencing (RRBS).
RESULTS
Methylated cytosine (mC) was found mostly in CpG dinucleotides, located mostly in the intronic, intergenic, and exonic regions. Forty intersected differentially methylated regions (DMRs) were identified in these 3 groups of samples. Thirteen differentially methylated genes with the same alteration trend were detected; these included , and . DMRs covering and were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways.
CONCLUSIONS
When compared to non-CSCs, cancer stem-like cells have a differential methylation status, which provides an important biological base for understanding esophageal CSCs and developing therapeutic targets for esophageal cancer.
背景
癌症干细胞（CSCs）被认为是癌症复发和转移的主要原因，而 DNA 甲基化参与了 CSCs 的维持。然而，食管 CSCs 的甲基化谱尚不清楚。
方法
从食管鳞状细胞癌（ESCC）细胞系 KYSE150 和 EC109 中分离出侧群（SP）细胞。从人原发性食管癌细胞中收集球体形成细胞。SP 细胞和球体形成细胞被用作癌症干细胞样细胞的替代物。我们使用简化重亚硫酸盐测序（RRBS）来研究食管癌细胞干细胞样细胞中的全基因组 DNA 甲基化谱。
结果
甲基化胞嘧啶（mC）主要位于 CpG 二核苷酸中，主要位于内含子、基因间和外显子区域。在这 3 组样本中，共鉴定出 40 个交叉差异甲基化区域（DMRs）。检测到 13 个具有相同改变趋势的差异甲基化基因，包括、和。覆盖和的 DMRs位于外显子中。这些差异甲基化基因参与了 10 类生物过程和 3 个细胞信号通路。
结论
与非 CSCs 相比，癌症干细胞样细胞具有不同的甲基化状态，这为理解食管 CSCs 并为食管癌开发治疗靶点提供了重要的生物学基础。
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