α7-Nicotinic Acetylcholine Receptor Promotes Cholangiocarcinoma Progression and Epithelial-Mesenchymal Transition Process.
Dig Dis Sci
; 64(10): 2843-2853, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-30949902
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 (α7-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 α7-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 α7-nAChR expression and clinicopathological characteristics. We used human cholangiocarcinoma cell lines QBC939 and RBE and α7-nAChR gene knockdown RBE cell lines generated by shRNA lentivirus transfection to investigate the biological functions of α7-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 α7-nAChR was high in cholangiocarcinoma tissues and was closely related to a shorter survival time in patients. α7-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 α7-nAChR knockdown. Moreover, nude mice xenograft experiments confirmed that α7-nAChR could promote cholangiocarcinoma in vitro. CONCLUSIONS: Overexpression of α7-nAChR induces cholangiocarcinoma progression by blocking apoptosis and promoting the EMT process. As an effective molecular biomarker and prognostic factor, α7-nAChR is a promising therapeutic target in cholangiocarcinoma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de los Conductos Biliares
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Colangiocarcinoma
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Proliferación Celular
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Receptor Nicotínico de Acetilcolina alfa 7
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Dig Dis Sci
Año:
2019
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos