Low vitamin D and high cholesterol facilitate oral carcinogenesis in 4NQO‐induced rat models via regulating glycolysis

Abstract Objectives Diets and nutritional habits are critical during carcinogenic processes, where a diet poor in fruits and vegetables and rich in meat and other foods of animal origin facilitates carcinogenesis. In this study, we aimed at investigating the possible involvement of vitamin D deficiency (VDD) and high cholesterol (HC) together in oral squamous cell carcinoma (OSCC) through modulating glycolysis. Subjects and Methods We compared total cholesterol, LDL, HDL, triglycerides, LDH, and vitamin D levels of OSCC patients and control individuals. We used GEO datasets for gene set enrichment and 4‐nitroquinoline‐1‐oxide induced in vivo oral carcinogenesis models to investigate contribution of VDD and HC during carcinogenesis via possible modulation of glycolysis. Results We found that VDD and HC co‐exist in OSCC patients, and deregulation of cholesterol and vitamin D levels results in enrichment of genes related to glycolysis. We, then, demonstrated that VDD and HC on their own and together facilitated the formation of larger tumors in 4NQO‐induced in vivo cancer models, which are suppressed by glycolysis inhibition. Conclusion We reported collaborative contribution of HC and VDD during oral carcinogenesis, which is mainly carried out via altering energy metabolism in tumor cells.