CEP55 as a promising biomarker and therapeutic target on gallbladder cancer

IntroductionGallbladder cancer (GBC) is a highly malignant biliary tumor with a poor prognosis. As existing therapies for advanced metastatic GBC are rarely effective, there is an urgent need to identify more effective targets for treatment. MethodsHub genes of GBC were identified by bioinformatics analysis and their expression in GBC was analyzed by tissue validation. The biological role of CEP55 in GBC cell and the underlying mechanism of the anticancer effect of CEP55 knockdown were evaluated via CCK8, colony formation assay, EDU staining, flow cytometry, western blot, immunofluorescence, and an alkaline comet assay. ResultsWe screened out five hub genes of GBC, namely PLK1, CEP55, FANCI, NEK2 and PTTG1. CEP55 is not only overexpressed in the GBC but also correlated with advanced TNM stage, differentiation grade and poorer survival. After CEP55 knockdown, the proliferation of GBC cells was inhibited with cell cycle arrest in G2/M phase and DNA damage. There was a marked increase in the apoptosis of GBC cells in the siCEP55 group. Besides, in vivo, CEP55 inhibition attenuated the growth and promoted apoptosis of GBC cells. Mechanically, the tumor suppressor effect of CEP55 knockdown is associated with dysregulation of the AKT and ERK signaling networks. DiscussionThese data not only demonstrate that CEP55 is identified as a potential independent predictor crucial to the diagnosis and prognosis of gallbladder cancer but also reveal the possibility for CEP55 to be used as a promising target in the treatment of GBC.

Automated summary

Through bioinformatics analysis, five key genes of GBC were identified, among which CEP55 was found to be overexpressed in GBC and associated with advanced TNM stage, differentiation grade, and poorer survival. Inhibition of CEP55 in GBC cells resulted in decreased proliferation, cell cycle arrest, DNA damage, and increased apoptosis. CEP55 inhibition in vivo attenuated tumor growth and promoted apoptosis in GBC cells. The tumor suppressor effect of CEP55 knockdown is mechanistically associated with dysregulation of the AKT and ERK signaling networks.