Choline-induced SLC5A7 impairs colorectal cancer growth by stabilizing p53 protein. (28th January 2022) - Yin, Yuan
Abstract: The members of the solute carrier (SLC) superfamily are vital membrane transporters in human cells. In the present study, we determine the expression and function of SLC5 family members in colorectal cancer (CRC). Expression analysis based on The Cancer Genome Atlas database and potential clinical relation analysis based on the Oncomine database indicate that SLC5A7 is downregulated and is predicted to correlate with the staging, and prognosis response of CRC. Additional results demonstrate that SLC5A7 is downregulated and correlates with good prognosis in patients with CRC. Ectopic expression of SLC5A7 either by overexpression, or uptake of choline efficiently inhibits CRC growth. Examination of the molecular mechanism reveals that SLC5A7 promotes p53 protein expression by directly interacting with and modifying p53 and disrupting the interaction between p53 and MDM2 in wild type p53 CRC cells. Our findings establish the clear correlation between SLC5A7 and tumour growth, providing a novel potential therapeutic target for CRC. Highlights: SLC5A7 is downregulated in CRC and related with good prognosis of patients. Ectopic expression of SLC5A7 efficiently inhibited CRC growth. SLC5A7 promotes p53 protein expression by directly interacting with p53 protein and disrupting the p53-MDM2 interaction. Choline uptake inhibits CRC growth by promoting SLC5A7 expression in p53 wild-type cells.