Staufen1 regulates DNA-demethylating agent-induced cell death via double-stranded RNA expression control in colorectal cancer cells

Abstract

5'-AZA-CdR (decitabine), known as a DNA-demethylation agent, is used as an anticancer agent for cancer such as colorectal cancer and acute myeloid leukemia. Recent studies have shown that decitabine abrogates the methylation of DNA regions that encoded endogenous retroviruses (ERVs) in cancer cells, resulting in an abnormal increase in intracellular ERV expression. Besides, these ERVs can make dsRNA structure form, leading to immune responses in cancer cells leading to apoptosis. However, unlike previous study results, some patients are not susceptible to chemotherapy. Moreover, dsRNAs that are abnormally increased by decitabine can interact with other dsRNA-binding proteins. Therefore there would be another critical factor that could exist. Through screening experiments to confirm the interaction effect between ERV and dsRNA binding proteins, we identified staufen1 as a protein that has a significant impact on the apoptotic mechanism of decitabine. Based on the results of this study, we expect to be able to realize patient-customized treatment with anticancer drugs.