The COL7A1/PI3K/AKT axis regulates the progression of cholangiocarcinoma

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 in vivo.

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.