CHPF promotes gastric cancer tumorigenesis through the activation of E2F1

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.

Analysis of Tumor Glycosylation Characteristics and Implications for Immune Checkpoint Inhibitor’s Efficacy for Breast Cancer

“…Some scholars validate that there are enriched mutations in B3GNT2 genes in colon cancer ( 30 ). CHPF is an important glycosyltransferase and participates in the biosynthesis of chondroitin sulfate ( 31 ). CHPF promotes BC growth, invasion, and metastasis by favoring 6- O -sulfated chondroitin sulfate formation in BC cells ( 32 ).…”

Characterization of glucose metabolism in breast cancer to guide clinical therapy

“…The pathologic opening of calcium channels leads to the continuous influx of calcium ions, which affects the division and proliferation of normal cells and causes the carcinogenesis of cells. CHPF is a common glycosyltransferase involved in the production of Chondroitin Sulfate in organisms ( 42 ). CHPF is highly expressed in lung adenocarcinoma and can promote tumor cell growth, invasion and metastasis, and inhibit tumor cell apoptosis ( 43 ).…”

Circular RNA circPFKP suppresses the proliferation and metastasis of gastric cancer cell via sponging miR-644 and regulating ADAMTSL5 expression

“…Following transfection, AGS and MKN45 cells were inoculated into 96-well plates at a density of 1,000 cells/well and cultivated at 37°C. Each well was supplemented with 10 μL of MTT solution (Dojindo, Kumamoto, Japan) at different time points (0, 24, 48, and 72 h) after incubation [ 23 ]. Then, the cells were cultured at 37°C for another 2 h, and the optical density (OD) value was examined at 490 nm with a microplate reader.…”

“…Transfected AGS and MKN45 cells were seeded in six-well plates (3 × 10 2 cells/well) and cultured at 37°C for two weeks. The culture medium was replaced every 3 d. After washing with phosphate-buffered saline (PBS), colonies were immobilized and stained with 0.1% crystal violet [ 23 ]. Finally, the cells were observed under a microscope.…”

“…At 24 h post-incubation, migrated cells were fixed with 4% paraformaldehyde and treated with 0.5% crystal violet. Images of the migrated cells were obtained using a microscope in five randomly selected fields [ 23 ].…”