BACKGROUND Esophageal squamous cell cancer (ESCC) is one kind of frequent digestive tumor. The inflammatory environment plays an important role in the tumorigenesis and development of ESCC. Cancer stem cells are a small group of tumor cells with stem cell characteristics, which can potentially hinder the tumor management and treatment. METHODS ELISA was performed to detect the lipopolysaccharide concentration in cancer tissues. qPCR, Western blot, FACS, Immunohistochemistry, Immunofluorescence and Dot blot were applied to detect target genes expression. CCK-8, Colony-formation, Transwell, Sphere and Xenograft were conducted to investigate the function of cells, influenced by risk factors. The survival curve was drawn with the Kaplan-Meier product limit estimator. Nano-hmC-Seal-seq was utilized to detect the downstream target of TET3. ChIP-qPCR was adopted to demonstrate the transcriptional regulation of stem cell-associated genes by HOXB2. RESULTS Lipopolysaccharide concentration was significantly up-regulated in ESCC. High concentration of lipopolysaccharide stimulation induced the stemness of ESCC cells. TET3 expression was elevated with lipopolysaccharide stimulation via p38/ERK-MAPK pathway in ESCC and negatively correlated with patients' survival. TET3 induced the stemness of ESCC cells. Nano-hmC-Seal-seq showed that TET3 overexpression led to a significant increase in 5hmC levels of HOXB2 gene region, which was thus identified as the downstream target of TET3. The binding of HOXB2 to NANOG and cMYC was verified by ChIP-qPCR. CONCLUSIONS Lipopolysaccharide served as a tumor promotor in ESCC by inducing cancer cell stemness through the activation of a LPS-TET3-HOXB2 signaling axis, which might provide a novel therapeutic strategy for ESCC. Video Abstract.

中文翻译：

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通过脂多糖-TET3-HOXB2信号传导轴在食管鳞状细胞癌中表观遗传诱导肿瘤干。

背景技术食管鳞状细胞癌（ESCC）是一种常见的消化道肿瘤。炎症环境在ESCC的肿瘤发生和发展中起重要作用。癌症干细胞是一小组具有干细胞特征的肿瘤细胞，可能会阻碍肿瘤的治疗和治疗。方法采用ELISA法检测癌组织中脂多糖的含量。采用qPCR，Western blot，FACS，免疫组织化学，免疫荧光和Dot印迹法检测靶基因的表达。进行了CCK-8，集落形成，Transwell，球形和异种移植，以研究受危险因素影响的细胞功能。用Kaplan-Meier乘积极限估计器绘制存活曲线。Nano-hmC-Seal-seq用于检测TET3的下游靶标。通过ChIP-qPCR来证明HOXB2对干细胞相关基因的转录调控。结果ESCC中脂多糖浓度明显上调。高浓度的脂多糖刺激诱导ESCC细胞的干性。通过ET38中的p38 / ERK-MAPK途径的脂多糖刺激，TET3的表达升高，并且与患者的生存呈负相关。TET3诱导胚胎干细胞干。Nano-hmC-Seal-seq表明，TET3过表达导致HOXB2基因区域5hmC水平显着增加，因此被确定为TET3的下游靶标。通过ChIP-qPCR验证了HOXB2与NANOG和cMYC的结合。结论脂多糖通过激活LPS-TET3-HOXB2信号轴诱导癌细胞干性，从而成为ESCC的肿瘤促进剂，可能为ESCC提供一种新的治疗策略。录像摘要。