Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, PR China.
Department of Medicine, The Hospital of Northeast Normal University, Changchun 130024, Jilin Province, PR China.
Int Immunopharmacol. 2023 May;118:110091. doi: 10.1016/j.intimp.2023.110091. Epub 2023 Apr 3.
Tumor microenvironment (TME) plays an important role in the progression of cholangiocarcinoma. This study aims to explore whether Mucin 1 (MUC1) regulates Foxp3 Treg cells in the TME of cholangiocarcinoma through the epidermal growth factor receptor (EGFR)/phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. High-throughput sequencing dataset in the GEO database combined with GeneCards and Phenolyzer databases was used to obtain key genes in cholangiocarcinoma, followed by downstream pathway prediction. The relationship among MUC1, EGFR, and PI3K/Akt signaling pathway was explored. CD4 T cells extracted from peripheral blood were induced to differentiate into Treg cells, followed by co-culture with cholangiocarcinoma cells. A mouse model was constructed to detect the role of MUC1 in the accumulation of Foxp3 Treg cells, malignant phenotypes of cholangiocarcinoma, and tumorigenesis in vivo. MUC1, highly expressed in cholangiocarcinoma, might be involved in cholangiocarcinoma development. MUC1 interacted with the EGFR to activate the EGFR/PI3K/Akt signaling pathway. MUC1 overexpression could activate the EGFR/PI3K/Akt signaling pathway, which promoted the accumulation of Foxp3 Treg cells in the TME and the malignant phenotypes of cholangiocarcinoma cells both in vitro and in vivo and enhanced tumorigenesis in vivo. MUC1 may interact with EGFR to activate the EGFR/PI3K/Akt signaling pathway, which induces the accumulation of Foxp3 Treg cells, enhancing the malignant phenotypes of cholangiocarcinoma cells and tumorigenesis in vivo and ultimately augmenting cholangiocarcinoma growth and metastasis.
肿瘤微环境（TME）在胆管癌的进展中起着重要作用。本研究旨在探讨黏蛋白 1（MUC1）是否通过表皮生长因子受体（EGFR）/磷酸肌醇-3-激酶（PI3K）/Akt 信号通路调节胆管癌细胞中的 Foxp3 Treg 细胞。利用 GEO 数据库中的高通量测序数据集，结合 GeneCards 和 Phenolyzer 数据库，获得胆管癌中的关键基因，然后进行下游通路预测。探讨了 MUC1、EGFR 和 PI3K/Akt 信号通路之间的关系。从外周血中提取 CD4 T 细胞，诱导其分化为 Treg 细胞，然后与胆管癌细胞共培养。构建小鼠模型，检测 MUC1 在 Foxp3 Treg 细胞积累、胆管癌细胞恶性表型和体内肿瘤发生中的作用。MUC1 在胆管癌中高表达，可能参与胆管癌的发生发展。MUC1 与 EGFR 相互作用激活 EGFR/PI3K/Akt 信号通路。MUC1 过表达可激活 EGFR/PI3K/Akt 信号通路，促进 TME 中 Foxp3 Treg 细胞的积累以及胆管癌细胞的恶性表型，在体内增强肿瘤发生。MUC1 可能与 EGFR 相互作用激活 EGFR/PI3K/Akt 信号通路，诱导 Foxp3 Treg 细胞的积累，增强胆管癌细胞的恶性表型和体内肿瘤发生，从而最终促进胆管癌的生长和转移。
