1. Chibby suppresses aerobic glycolysis and proliferation of nasopharyngeal carcinoma via the Wnt/β-catenin-Lin28/let7-PDK1 cascade.
- Author
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Cai CF, Ye GD, Shen DY, Zhang W, Chen ML, Chen XX, Han DX, Mi YJ, Luo QC, Cai WY, and Yang SY
- Subjects
- Aerobiosis, Animals, Cell Line, Tumor, Cell Proliferation, Disease Models, Animal, Female, Glycolysis, Heterografts, Humans, Immunohistochemistry, Mice, Nasopharyngeal Carcinoma pathology, Protein Binding, Protein Serine-Threonine Kinases metabolism, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, RNA-Binding Proteins genetics, Signal Transduction, Wnt Proteins genetics, beta Catenin genetics, Carrier Proteins metabolism, MicroRNAs genetics, Nasopharyngeal Carcinoma genetics, Nasopharyngeal Carcinoma metabolism, Nuclear Proteins metabolism, Protein Serine-Threonine Kinases genetics, RNA-Binding Proteins metabolism, Wnt Proteins metabolism, beta Catenin metabolism
- Abstract
Background: Great progress has been achieved in the study of the aerobic glycolysis or the so-called Warburg effect in a variety of cancers; however, the regulation of the Warburg effect in Nasopharyngeal carcinoma (NPC) has not been completely defined., Methods: Gene expression pattern of NPC cells were used to test associations between Chibby and β-catenin expression. Chibby siRNAs and over-expression vector were transfected into NPC cells to down-regulate or up-regulate Chibby expression. Loss- and gain-of function assays were performed to investigate the role of Chibby in NPC cells. Western blot, cell proliferation, Glucose uptake, Lactate release, ATP level, and O2 consumption assays were used to determine the mechanism of Chibby regulation of underlying targets. Finally, immunohistochemistry assay of fresh NPC and nasopharyngeal normal tissue sample were used to detect the expression of Chibby, β-Catenin, and PDK1 by immunostaining., Results: We observed that Chibby, a β-catenin-associated antagonist, is down-regulated in nasopharyngeal carcinoma cell lines and inhibits Wnt/β-Catenin signaling induced Warburg effect. Mechanism study revealed that Chibby regulates aerobic glycolysis in NPC cells through pyruvate dehydrogenase kinase 1(PDK1), an important enzyme involved in glucose metabolism. Moreover, Chibby suppresses aerobic glycolysis of NPC via Wnt/β-Catenin-Lin28/let7-PDK1 cascade. Chibby and PDK1 are critical for Wnt/β-Catenin signaling induced NPC cell proliferation both in vitro and in vivo. Finally, immunostaining assay of tissue samples provides an important clinical relevance among Chibby, Wnt/β-Catenin signaling and PDK1., Conclusions: Our study reveals an association between Chibby expression and cancer aerobic glycolysis, which highlights the importance of Wnt/β-catenin pathway in regulation of energy metabolism of NPC. These results indicate that Chibby and PDK1 are the potential target for NPC treatment.
- Published
- 2018
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