Enhanced Radiosensitivity of Esophagus Cancer through Loss of ADAR1 and Cell Apoptosis via NF-kB Signaling Pathway

Abstract

RNA editing is a common posttranslational mechanism for generating genomic diversity by modifying selected RNA sequences without altering the genome. A new understanding of cancer therapy can be enhanced by the discovery of ADAR1 in the control of signal transduction pathways. However, the study of the biological effects of ADAR1 in radioresistance of esophageal cancer is not very deep. The TCGA data sets were used to explore the correlations between ADAR1 and prognosis in esophageal cancer. Two pairs of ADAR1 gene siRNA fragments (siADAR1-1 and siADAR1-2) were designed and transiently transfected into KYSE410 cells and KYSE410-RT cells. The expression of ADAR1 was detected by RT-PCR and WB. Colony formation assay was used to evaluate the radiosensitivity. Apoptosis was measured using a flow cytometric apoptosis assay. Furthermore, transcriptome sequencing was performed to elucidate the pathways regulated by ADAR1. In this study, we found that ADAR1 is overexpressed in esophageal tumors and is associated with poor prognosis in bioinformatics analysis. Colony formation experiment showed that siRNA-mediated depletion of ADAR1 in KYSE410 cells could inhibit cell proliferation and reduce radiosensitivity significantly. Consistently results were showed in KYSE410-RT cells. Mechanism studies revealed loss of ADAR1 induced cell apoptosis and radiotherapy could enhance this process. Transcriptomic data indicated that ADAR1 could regulate apoptosis through the NF-kB pathway. RNA editing was found to be involved in the regulation of radiosensitivity of esophageal cancer and loss of ADAR1 can cause cell apoptosis though NF-kB pathway. A better understanding of A-to-I RNA editing and its oncogenic mechanisms may facilitate the development of radiotherapy in esophageal cancer.