Rs13293512 polymorphism located in the promoter region of let‐7 is associated with increased risk of radiation enteritis in colorectal cancer

摘要

Abstract RE (Radiation enteritis) has been characterized by the inflammation reaction, and in this study, we aim to explore inflammatory cytokines and underlying mechanism involved in the pathogenesis of RE. Luciferase assay was performed to explore whether polymorphism affected the expression of let‐7, and also validated let‐7 directly regulated f IL‐6 expression. Then Elisa was performed to study the mechanism of rs13293512 polymorphism associated with enteritis occurrence. And Western‐blot and real‐time PCR were performed to verify the relationship between let‐7 and IL‐6. 380 colorectal cancer patients were recruited, and all participants were genotyped. We found that occurrence probability of enteritis patients carried CC genotype (32%) was much higher than that in TT and TC groups (15%). In addition, we showed that the presence of the minor (C) allele of the polymorphism in the promoter region of let‐7 substantially reduced the transcription activity of let‐7, furthermore, we validated that let‐7 directly regulated IL‐6 expression by using luciferase reporter system. Moreover, IL‐6 was highly expressed in peripheral blood and colonic mucosa samples genotyped as CC compared to those in TT and TC groups, furthermore, IL‐6 was highly expressed in peripheral blood and colonic mucosa samples from participants with enteritis than without enteritis, whereas let‐7 was highly expressed in peripheral blood and colonic mucosa samples genotyped as TT and TC compared to those in CC groups. Let‐7 polymorphism (rs13293512) was associated with risk of RE in the colorectal cancer patients who received radiotherapy.