Abstract
Chondroitin polymerizing factor (CHPF) is an important glycosyltransferase involved in the biosynthesis of chondroitin sulfate. However, the relationship between CHPF and gastric cancer has not been fully investigated. CHPF expression in gastric cancer tissues was detected by immunohistochemistry and correlated with gastric cancer patient prognosis. Cultured gastric cancer cells and human gastric epithelial cell line GES1 were used to investigate the effects of shCHPF and shE2F1 on the development and progression of gastric cancer by MTT, western blotting, flow cytometry analysis of cell apoptosis, colony formation, transwell and gastric cancer xenograft mouse models, in vitro and in vivo. In gastric cancer tissues, CHPF was found to be significantly upregulated, and its expression correlated with tumor infiltration and advanced tumor stage and shorter patient survival in gastric cancer. CHPF may promote gastric cancer development by regulating cell proliferation, colony formation, cell apoptosis and cell migration, while knockdown induced the opposite effects. Moreover, the results from in vivo experiments demonstrated that tumor growth was suppressed by CHPF knockdown. Additionally, E2F1 was identified as a potential downstream target of CHPF in the regulation of gastric cancer, and its knockdown decreased the CHPF-induced promotion of gastric cancer. Mechanistic study revealed that CHPF may regulate E2F1 through affecting UBE2T-mediated E2F1 ubiquitination. This study showed, for the first time, that CHPF is a potential prognostic indicator and tumor promoter in gastric cancer whose function is likely carried out through the regulation of E2F1.
Highlights
Gastric cancer (GC), one of the most commonly diagnosed malignant tumors, has the fifth highest incidence rate and the third highest mortality rate among all cancer types [1, 2]
The results demonstrated that Chondroitin polymerizing factor (CHPF) was upregulated in gastric cancer tissues compared with normal tissues, and a high CHPF expression level was correlated with Tumor cell infiltration, advanced tumor stage, and poor prognosis
CHPF was upregulated in gastric cancer and associated with a poor prognosis CHPF expression in clinical specimens was detected by immunohistochemical analysis to explore the role of CHPF in gastric cancer
Summary
Gastric cancer (GC), one of the most commonly diagnosed malignant tumors, has the fifth highest incidence rate and the third highest mortality rate among all cancer types [1, 2]. Comprehensive therapy based on surgery is the most effective strategy for the treatment of gastric cancer [3, 4]. Due to the atypical early symptoms of gastric cancer, most gastric cancer patients are diagnosed with advanced-stage tumors, which decreases the chance of resection and results in a poor 5-year survival rate [5]. The therapeutic effect in gastric cancer has improved with the emergence of targeted drugs developed based on molecular biology research of gastric cancer [7], the 5-year survival rate of gastric cancer has not improved satisfactorily [4]. There is an urgent need to further explore the molecular mechanism of gastric cancer to develop novel biomarkers and therapeutic targets, which will help to overcome the limitations associated with the diagnosis and treatment of gastric cancer
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