胞苷脱氨酶通过通过NFκB信号调节上皮 - 间质转变来增强肝癌侵袭
Cytidine deaminase enhances liver cancer invasion by modulating epithelial-mesenchymal transition via NFκB signaling
影响因子:4.40000
分区:医学3区 / 生化与分子生物学3区 医学：研究与实验3区
发表日期:2024 Sep 19
作者:
Chia-Jung Liao, Yang-Hsiang Lin, Huei-Tzu Chien, Yi-Wen Wang, Tzu-Kang Lin, Chau-Ting Yeh, Kwang-Huei Lin
摘要
癌症转移是与癌症相关死亡的主要原因，强调了了解其潜在机制的重要性。肝细胞癌（HCC）是一种高度恶性的癌症，被选为我们的研究模型。我们的目的是使用体外和体内选择策略开发高度转移细胞系，并通过与良好的细胞表现出高度良好的细胞表现出色的细胞表现出了相当大的细胞。微阵列分析鉴定出与全身化学疗法耐药性相关的胞苷脱氨酶（CDA），是高度转移细胞中过表达的基因之一。癌症基因组图集计划的数据分析表明，尽管CDA在HCC中被下调，但CDA表达高的患者的预后较差。细胞模型证实CDA的过表达增强了细胞迁移和侵袭，而CDA敲低抑制了这些能力。研究了上皮 - 间质转化（EMT）涉及的关键分子，我们发现CDA过表达增加了Fascin，N-钙粘蛋白，β-catenin和Snail的表达，同时降低E-钙粘蛋白的表达。相反，CDA敲低产生了相反的结果。此外，我们发现CDA调节了控制N-钙粘着蛋白的表达的NF-κB信号，从而促进了HCC细胞的浸润能力。我们隔离了高度转移性细胞，并鉴定了潜在的HCC转移相关基因。 CDA通过通过NF-κB途径调节EMT来促进细胞侵袭。有必要进行未来的研究，以探索CDA作为预后和治疗决策的生物标志物的潜力。
Abstract
Cancer metastasis is the leading cause of cancer-related deaths, underscoring the importance of understanding its underlying mechanisms. Hepatocellular carcinoma (HCC), a highly malignant type of cancer, was selected as our research model.We aimed to develop high-metastatic cell lines using in vitro and in vivo selection strategies and identify critical metastasis-related genes through microarray analyses by comparing them with parental cells.Our results showed that the high-metastatic cell lines exhibited significantly stronger invasion abilities than parental cells. Microarray analyses identified cytidine deaminase (CDA), a gene associated with systemic chemotherapy resistance, as one of the overexpressed genes in the high-metastatic cells. Data analysis from The Cancer Genome Atlas Program revealed that while CDA is downregulated in HCC, patients with high CDA expression tend to have poorer prognoses. Cell models confirmed that CDA overexpression enhances cell migration and invasion, whereas CDA knockdown inhibits these abilities. Investigating the key molecules involved in the epithelial-mesenchymal transition (EMT), we found that CDA overexpression increases the expression of fascin, N-cadherin, β-catenin, and snail while decreasing E-cadherin expression. Conversely, CDA knockdown produced opposite results. Additionally, we discovered that CDA regulates NF-κB signaling, which controls the expression of N-cadherin, thereby promoting the invasion capability of HCC cells.We isolated highly metastatic cells and identified potential HCC metastasis-related genes. CDA promotes cell invasion by regulating EMT through the NF-κB pathway. Future studies are warranted to explore the potential of CDA as a biomarker for prognosis and therapeutic decision-making.