Zhou Shuo, Yang Yuhang, Qi Feiyu, Sun Wanliang, Zhang Dengyong, Lu Zheng, Chen Yongliang
School of Medicine, Nankai University, Tianjin, 300071, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, China.
Sci Rep. 2025 Jan 4;15(1):817. doi: 10.1038/s41598-025-85241-6.
Cholangiocarcinoma (CCA), a highly aggressive form of cancer, is known for its high mortality rate. A Disintegrin and Metalloprotease Domain-like Protein Decysin-1 (ADAMDEC1) can promote the development and metastasis in various tumors by degrading the extracellular matrix. However, its regulatory mechanism in CCA remains unclear. Public databases and clinical tissue samples were used to evaluate whether ADAMDEC1 expression was correlated with the prognosis of CCA. We investigated the expression of ADAMDEC1-related regulatory genes and proteins in CCA and assessed the biological behaviors of CCA cells in vitro through functional experiments. Meanwhile, the interacting proteins of ADAMDEC1 and its involvement in the nuclear factor-kappa B (NF-κB) signaling pathway were screened and verified through bioinformatics analysis. The tumorigenicity of CCA was also assessed in a xenograft nude mouse model. Our results showed that ADAMDEC1 was highly expressed in tumor tissues from CCA patients and was positively correlated with poor prognosis. Interference cell lines targeting ADAMDEC1 in CCA cells were successfully constructed. Knockdown of ADAMDEC1 or MMP12 both affected the biological behaviors of CCA cells, and ADAMDEC1 silencing inhibited tumorigenicity and tumor growth of CCA in vivo. Moreover, ADAMDEC1 interacted with MMP12, modulating its expression and promoting the activation of the NF-κB signaling pathway. Our study uncovered the expression patterns and functional roles of ADAMDEC1 in CCA cells and tissues, highlighting its connection to the NF-κB pathway and MMP12 in the development of CCA. Therefore, ADAMDEC1 may serve as a potential therapeutic target for CCA.
胆管癌（CCA）是一种侵袭性很强的癌症，以其高死亡率而闻名。一种去整合素和金属蛋白酶结构域样蛋白Decysin-1（ADAMDEC1）可通过降解细胞外基质促进各种肿瘤的发生发展和转移。然而，其在CCA中的调控机制仍不清楚。我们利用公共数据库和临床组织样本评估ADAMDEC1表达是否与CCA的预后相关。我们研究了CCA中ADAMDEC1相关调控基因和蛋白的表达，并通过功能实验评估了CCA细胞在体外的生物学行为。同时，通过生物信息学分析筛选并验证了ADAMDEC1的相互作用蛋白及其在核因子-κB（NF-κB）信号通路中的作用。我们还在异种移植裸鼠模型中评估了CCA的致瘤性。我们的结果表明，ADAMDEC1在CCA患者的肿瘤组织中高表达，且与不良预后呈正相关。成功构建了靶向CCA细胞中ADAMDEC1的干扰细胞系。敲低ADAMDEC1或MMP12均影响CCA细胞的生物学行为，沉默ADAMDEC1可抑制CCA在体内的致瘤性和肿瘤生长。此外，ADAMDEC1与MMP12相互作用，调节其表达并促进NF-κB信号通路的激活。我们的研究揭示了ADAMDEC1在CCA细胞和组织中的表达模式及功能作用，突出了其在CCA发生发展中与NF-κB通路和MMP12的联系。因此，ADAMDEC1可能成为CCA的一个潜在治疗靶点。
