α7-Nicotinic Acetylcholine Receptor Promotes Cholangiocarcinoma Progression and Epithelial-Mesenchymal Transition Process

Background Cholangiocarcinoma is one of the most deadly malignant tumors characterized by a tendency of local invasiveness and metastasis at the early phase, high recurrence rate, and difficulty in treatment. Alpha7-nicotinic acetylcholine receptor (alpha 7-nAChR) is highly expressed in a variety of tumors, including cholangiocarcinoma, and may promote tumor progression, but the mechanisms are largely unknown. Aims Our study is the first to expound upon the role that alpha 7-nAChR plays in cholangiocarcinoma. Methods We assessed 50 human cholangiocarcinoma tissue samples and 20 normal biliary samples using immunohistochemical staining to find the correlation between alpha 7-nAChR expression and clinicopathological characteristics. We used human cholangiocarcinoma cell lines QBC939 and RBE and alpha 7-nAChR gene knockdown RBE cell lines generated by shRNA lentivirus transfection to investigate the biological functions of alpha 7-nAChR in proliferation, apoptosis, migration, and invasiveness in vitro. Further, western blotting was used to detect apoptosis and epithelial-mesenchymal transition (EMT)-related signaling proteins. Cholangiocarcinoma xenografts in nude mice were used for tumorigenicity assays in vivo. Results The expression of alpha 7-nAChR was high in cholangiocarcinoma tissues and was closely related to a shorter survival time in patients. alpha 7-nAChR knockdown decreased cell proliferation ability, increased early apoptosis, and weakened cell migration and invasion. Apoptosis-related proteins and components of the EMT process were altered after alpha 7-nAChR knockdown. Moreover, nude mice xenograft experiments confirmed that alpha 7-nAChR could promote cholangiocarcinoma in vitro. Conclusions Overexpression of alpha 7-nAChR induces cholangiocarcinoma progression by blocking apoptosis and promoting the EMT process. As an effective molecular biomarker and prognostic factor, alpha 7-nAChR is a promising therapeutic target in cholangiocarcinoma.