Agrin expression is correlated with tumor development and poor prognosis in cholangiocarcinoma

Objective This study examined the role of agrin in the development of cholangiocarcinoma (CCA). Methods Western blotting was performed to detect the expression of target genes. The correlation between agrin expression and prognosis was analyzed using the Kaplan–Meier method. Proliferation, migration...

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Bibliographic Details
Published in:Journal of international medical research 2021-05, Vol.49 (5), p.3000605211009722-3000605211009722
Main Authors: He, Meimei, Cheng, Chen, Tu, Junxue, Ji, Sha-Sha, Lou, Dan, Bai, Binglong
Format: Article
Language:English
Subjects:
Agrin
Animals
Bile Duct Neoplasms - genetics
Bile Ducts, Intrahepatic
Cell cycle
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cholangiocarcinoma
Cholangiocarcinoma - genetics
Gene Expression Regulation, Neoplastic
Medical prognosis
Mice
Pre-Clinical Research Report
Prognosis
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Summary:Objective This study examined the role of agrin in the development of cholangiocarcinoma (CCA). Methods Western blotting was performed to detect the expression of target genes. The correlation between agrin expression and prognosis was analyzed using the Kaplan–Meier method. Proliferation, migration, invasion, and tumorigenesis were examined in CCA cells and tissues using the Cell Counting Kit-8 assay, cell cycle analysis, transwell migration assay, and nude mouse tumorigenicity assay in vivo, respectively. Results Agrin expression was significantly upregulated in CCA tissues compared with that in adjacent non-tumor tissues, and agrin expression was correlated with poorer tumor characteristics such as portal vein tumor thrombus, intrahepatic metastasis, and worse survival. Forced agrin expression in CCA cells apparently promoted proliferation, colony formation, migration, invasion, and cell cycle progression, but agrin depletion had the opposite effects. Furthermore, agrin-depleted CCA cells developed fewer and smaller tumors than control cells in vivo. Mechanistic analyses indicated that agrin activated the Hippo signaling pathway and induced the translocation of YAP to the nucleus. Conclusions Agrin promoted CCA progression by activating the Hippo signaling pathway, suggesting its promise as a target for CCA therapy.
ISSN:0300-0605
1473-2300
DOI:10.1177/03000605211009722