Journal of Cell Biology (JCB)
Journal of Cell Biology (JCB)
5 years ago

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

Zhang HongLian, Xiao ZhiGang, Dong HongYu, Huang ZhongCheng, Liu Qi
Background: 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. Method: 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. Results: 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. Conclusion: Let-7 polymorphism (rs13293512) was associated with risk of RE in the colorectal cancer patients who received radiotherapy. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26733

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