Ma Yang, Zhang Yanfang, Chen Fangfang, Liu Sihua, Wang Dongdong, Lu Zheng, Zhang Dengyong, Liang Rui
Department of General Surgery, The First Affiliated Hospital of BengBu Medical College, NO. 287, Changhuai Road, Longzihu district, Bengbu, 233000, Anhui, China.
Heliyon. 2024 Sep 7;10(18):e37361. doi: 10.1016/j.heliyon.2024.e37361. eCollection 2024 Sep 30.
The role and molecular mechanisms of collagen type VII (COL7A1) in cholangiocarcinoma (CCA) remain unknown.
We analyzed the expression of COL7A1 in CCA and its relationship with patient prognosis using bioinformatic techniques. Expression levels of COL7A1 in CCA cells and tissues were detected using reverse transcription-quantitative PCR, western blotting, and immunohistochemistry. The effects of COL7A1 expression on the proliferation, migration, and invasion of CCA cells were assessed using CCK-8, colony formation, and Transwell assays. Bioinformatics and luciferase reporter gene assays were performed to examine the binding of KLF4 to COL7A1, and cytological experiments further verified the role of KLF4 in regulating the CCA phenotype through COL7A1. Xenograft mouse models were established to investigate the effects of COL7A1 on CCA tumor growth .
CCA tissues exhibited higher COL7A1 expression than normal bile duct tissues. There was no significant correlation between high or low COL7A1 expression and the survival time of patients with CCA. COL7A1 knockdown inhibited CCA cell proliferation, migration, and invasion. Furthermore, COL7A1 knockdown suppressed the activation of the PI3K/AKT signaling pathway. KLF4 can bind to COL7A1 and regulate COL7A1 expression, which in turn regulates the PI3K/AKT signaling pathway and impacts the proliferation and metastasis of CCA cells.
Our findings suggest that KLF4 regulates CCA cell proliferation, migration, and invasion via the COL7A1/PI3K/AKT axis.
VII型胶原蛋白（COL7A1）在胆管癌（CCA）中的作用及分子机制尚不清楚。
我们使用生物信息学技术分析了COL7A1在CCA中的表达及其与患者预后的关系。采用逆转录定量PCR、蛋白质免疫印迹法和免疫组织化学法检测COL7A1在CCA细胞和组织中的表达水平。使用CCK-8、集落形成和Transwell实验评估COL7A1表达对CCA细胞增殖、迁移和侵袭的影响。进行生物信息学和荧光素酶报告基因实验以检测KLF4与COL7A1的结合，细胞学实验进一步验证了KLF4通过COL7A1调节CCA表型的作用。建立异种移植小鼠模型以研究COL7A1对CCA肿瘤生长的影响。
CCA组织中COL7A1表达高于正常胆管组织。COL7A1表达的高低与CCA患者的生存时间无显著相关性。COL7A1敲低抑制了CCA细胞的增殖、迁移和侵袭。此外，COL7A1敲低抑制了PI3K/AKT信号通路的激活。KLF4可与COL7A1结合并调节COL7A1表达，进而调节PI3K/AKT信号通路并影响CCA细胞的增殖和转移。
我们的研究结果表明，KLF4通过COL7A1/PI3K/AKT轴调节CCA细胞的增殖、迁移和侵袭。
