The Role And Mechanism Of Lipid Metabolism Related Gene LPCAT1 To Enhance Sensitivity Of Colorectal Cancer To Oxaliplatin

Background: Colorectal cancer has become an important global health problem due to its high morbidity,mortality and the rising incidence of CRC at younger ages.Oxaliplatin is an effective first-line therapy for colorectal cancer,but chemoresistance is the most important cause of CRC treatment failure for oxaliplatin therapy.To elucidate the pathogenesis of colorectal cancer and the molecular mechanism of chemoresistance has become a focus of current research.As one of the main features of cancer,abnormal lipid metabolism is closely related to chemoresistance.At present,there are many studies have reported LPCAT1 as a potential tumor-promoting gene in colorectal cancer,but its effect and mechanisms on chemosensitivity have not been elucidated.Objective: To explore the effect and molecular mechanisms of lipid metabolism-related gene LPCAT1 on the chemosensitivity of oxaliplatin in colorectal cancer.Methods: After knockdown of LPCTA1,proliferation,apoptosis and oxidative stress level were measured by MTS assay,Ed U,Flow cytometry and subcutaneous xenograft tumor assay.Using lipidomic analysis to determine the role of LPCAT1 and OXA on metabolic profiles in CRC.Using transcriptomic to analyze the enrichment of differentially expressed genes before and after knockdown of LPCAT1 and treated with OXA,in order to explore the mechanism by which LPCAT1 affects OXA chemoresistance in CRC.Results:(1)Knockdown of LPCAT1 promoted resistance to OXA chemotherapy in CRC cells.In vivo subcutaneous tumorigenesis experiments showed that LPCAT1 knockdown inhibits tumor growth.(2)LPCAT1 depletion significantly reduced saturated PC,while knockdown LPCAT1 with OXA-treated significantly up-regulated polyunsaturated TAG.(3)RNA-Seq showed that LPCAT1 may regulate the sensitivity of CRC to OXA chemotherapy through the cytokine-cytokine receptor interaction pathway.Conclusion: LPCAT1 promotes the chemosensitivity of OXA in CRC by regulating lipid metabolism and then affecting the cytokinecytokine receptor interaction pathway.