Guo Xiaojuan, Wang Jinxi, Tian Yunxiao, Yang Jianhua, Wu Shiqian, Xin Lihui, Feng Zhe, Niu Guangxu
Department of Pathology, Handan Center Hospital, Handan, 056002, China.
The Fourth Department of General Surgery, The First Hospital of Handan, Handan, 056002, China.
Heliyon. 2024 Jun 15;10(12):e32528. doi: 10.1016/j.heliyon.2024.e32528. eCollection 2024 Jun 30.
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.
我们旨在研究胆管癌（CCA）中微小RNA（miRNA）的失调情况，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因子，靶向各种信号通路。本研究旨在探讨miR-125a-3在CCA中的表达水平、表观遗传机制及功能。研究数据表明，miR125a-3p在CCA组织样本和细胞系中的表达水平降低，且与淋巴结转移、组织分化及TNM分期密切相关。数据表明，miR-125a-3p表达降低与胆管癌患者预后较差密切相关。miR-125a-3p通过抑制CCA细胞的活力、迁移和侵袭发挥肿瘤抑制作用。miR-125a-3p基因启动子区域存在CpG岛，miR-125a-3p基因启动子区域的甲基化导致miR-125a-3p的转录抑制。此外，在下游机制中，miR125a-3p可靶向调控CAC1 mRNA和蛋白表达，而CAC1的高表达可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。机制上，miR-125a-3p作为肿瘤抑制因子，通过靶向CAC1基因表达参与CCA的发生发展。因此，miR-125a-3p可能成为CCA诊断、预后评估或分子治疗的新靶点。
