我们的目的是研究胆管癌 (CCA) 中 microRNA (miRNA) 的失调，包括其对转录组稳态和细胞行为的影响。 miRNA 作为转录输出的有效表观遗传调节剂，针对各种信号通路。本研究旨在探讨miR-125a-3在CCA中的表达水平、表观遗传机制和功能。研究数据显示，CCA组织样本和细胞系中miR125a-3p的表达水平降低，且与淋巴结转移、组织分化和TNM分期密切相关。数据表明，胆管癌患者的 miR-125a-3p 表达降低与预后较差之间存在密切相关。 miR-125a-3p 通过抑制 CCA 细胞的活力、迁移和侵袭来充当肿瘤抑制剂。 miR-125a-3p基因启动子区存在CpG岛，miR-125a-3p基因启动子区甲基化导致miR-125a-3p转录抑制。此外，miR125a-3p在下游机制中能够靶向调控CAC1 mRNA和蛋白的表达，CAC1的高表达能够促进胆管癌细胞的增殖、迁移和侵袭。这些数据表明 miR-125a-3p 启动子甲基化导致其表达沉默。从机制上讲，miR-125a-3p作为肿瘤抑制因子，通过靶向CAC1基因表达参与CCA的发生和发展。因此，miR-125a-3p可能作为CCA诊断、预后评估或分子治疗的新靶点。© 2024 作者。

We aimed to investigate the dysregulation of the microRNAs(miRNAs) in cholangiocarcinoma (CCA), including its impact on the homeostasis of the transcriptome and cellular behavior. MiRNAs serve as potent epigenetic regulators of transcriptional output, targeting various signaling pathways. This study aimed to investigate the expression level, epigenetic mechanism and function of miR-125a-3 in CCA. The study data showed that the expression level of miR125a-3p was decreased in CCA tissue samples and cell lines, and it was closely related to lymph node metastasis, tissue differentiation and TNM stage. The data demonstrate a strong association between decreased miR-125a-3p expression and poorer prognosis in cholangiocarcinoma patients. miR-125a-3p acts as a tumor suppressor by inhibiting the viability, migration and invasion of CCA cells. There are CpG islands in the promoter region of miR-125a-3p gene, and the methylation of the promoter region of miR-125a-3p gene leads to the transcriptional repression of miR-125a-3p. In addition, miR125a-3p can target and regulate CAC1 mRNA and protein expression in the downstream mechanism, and the high expression of CAC1 can promote the proliferation, migration and invasion of cholangiocarcinoma cells. These data demonstrate that miR-125a-3p promoter methylation leads to silencing of its expression. Mechanically, miR-125a-3p acts as a tumor suppressor and participates in the occurrence and development of CCA through targeting CAC1 gene expression. Therefore, miR-125a-3p may serve as a new target for the diagnosis, prognostic assessment or molecular therapy of CCA.© 2024 The Author(s).