Interferon regulatory factor-1 suppresses DNA damage response and reverses chemotherapy resistance by downregulating the expression of RAD51 in gastric cancer.

ABSTRACT: Recent studies have shown that IRF-1 plays a significant role in various tumour-induced chemoresistance, but its role and mechanism in gastric cancer-associated chemoresistance are not clear. Our study showed that IRF-1 expression could reverse gastric cancer-related chemoresistance. Dysregulated DNA repair is an important cause of chemoresistance. We established a chemoresistant gastric cancer cell line and found that drug-resistant gastric cancer cells had increased DNA repair ability and that IRF-1 regulated DNA damage repair. Further studies showed that IRF-1 inhibited the expression of RAD51 directly by binding to the RAD51 promoter to affect DNA damage repair; this binding reversed resistance. However, restoring the expression of RAD51 halted the inhibitory effect of IRF-1 partially.

SUBMITTER: Tan L 

PROVIDER: S-EPMC7191096 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature