Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer.

Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer.
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DOI:
10.1177/1533033820983793
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发表时间:
2020-01
影响因子:
2.8
通讯作者:
Jiang W
Jiang W
中科院分区:
医学4区
文献类型:
--
作者:
Yu X;Teng Y;Jiang X;Yuan H;Jiang W

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癌症干细胞(CSCs)被认为是癌症复发和转移的主要原因,且DNA甲基化参与维持癌症干细胞。然而,食管癌症干细胞的甲基化图谱仍不明确。 从食管鳞状细胞癌(ESCC)细胞系KYSE150和EC109中分离出旁群(SP)细胞。从人原发性食管癌细胞中收集成球细胞。SP细胞和成球细胞被用作类癌症干细胞的替代物。我们采用简化代表性亚硫酸氢盐测序(RRBS)研究了食管类癌症干细胞的全基因组DNA甲基化图谱。 发现甲基化胞嘧啶(mC)大多存在于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组样本中鉴定出40个交叉的差异甲基化区域(DMRs)。检测到13个具有相同变化趋势的差异甲基化基因,包括OTX1、SPACA1、CD163L1、ST8SIA2、TECR、CADM3、GRM1、LRRK1、CHSY1、PROKR2、LINC00658、LOC100506688和NKD2。覆盖ST8SIA2和GRM1的DMRs位于外显子中。这些差异甲基化基因参与10类生物学过程和3条细胞信号通路。 与非癌症干细胞相比,类癌症干细胞具有不同的甲基化状态,这为理解食管癌症干细胞以及开发食管癌治疗靶点提供了重要的生物学基础。
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. 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). 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 OTX1, SPACA1, CD163L1, ST8SIA2, TECR, CADM3, GRM1, LRRK1, CHSY1, PROKR2, LINC00658, LOC100506688, and NKD2. DMRs covering ST8SIA2 and GRM1 were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways. 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.
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