![]() Recent work has shown that SQLE is overexpressed in CRC 8 10 11 nevertheless, the potential role of SQLE in CRC initiation and progression remains controversial. Squalene epoxidase (SQLE) is a rate-limiting enzyme in cholesterol biosynthesis. Nevertheless, lipid metabolism-dependent molecular mechanisms involved in CRC remains poorly understood. 4 Fatty acids, 5 6 cholesterol 7 8 and bile acids 9 have been implicated in CRC pathogenesis. 3 Lipid accumulation promotes CRC through increased reactive oxygen species and MAPK signalling. 1 2 Epidemiological studies also suggest a high dietary fat intake to increased risk of CRC. Both obesity and serum lipids are risk factors for CRC. Hence, it is important to identify novel genes involved in the pathogenesis of CRC in order to develop effective treatments, either alone or in combination with chemotherapy.Īberrant lipid metabolism is increasingly considered a hallmark characteristic of many cancers, including CRC. Patients with advanced CRC with metastasis still suffer from poor prognosis and drug resistance severely diminishes the therapeutic efficacy of chemotherapy. Both the incidence and mortality of CRC are still increasing in young people, especially in low-income and middle-income countries. Finally, we demonstrated that terbinafine, a SQLE inhibitor, could be repurposed for CRC by synergising with oxaliplatin and 5-fluorouracil to inhibit CRC growth.Ĭolorectal cancer (CRC) is the third most common cancer and ranks the second in terms of cancer mortality worldwide. Transplantation of Sqle tg mice stool to germ-free mice impaired gut barrier function and stimulated cell proliferation compared with control mice stool. Consistent with detrimental effect of secondary bile acids, gut barrier function was impaired in Sqle tg mice, with reduced tight junction proteins Jam-c and occludin. Integrative metagenomic and metabolomic analyses unveiled gut dysbiosis in Sqle tg mice with enriched pathogenic bacteria, which was correlated to increased secondary bile acids. In azoxymethane-induced CRC model, Sqle tg mice showed increased tumourigenesis compared with wild-type mice (p<0.01). SQLE promoted CRC cell proliferation by inducing cell cycle progression and suppressing apoptosis. Results SQLE messenger RNA and protein expression was upregulated in CRC (p<0.01) and predict poor survival of patients with CRC. ![]() 4 Lee Kong Chian School of Medicine, Nanyang Technological University, Singaporeĭr Jun Yu, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.3 Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong SAR, China.2 Department of Laboratory Animal Science, College of Basic Medical Sciences, Army Medical University, Chongqing, China.1 Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China. ![]()
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