Upregulation of exonuclease 1 caused by homology-dependent repair confers cisplatin resistance to gastric cancer cells.

The homology-dependent repair (HDR) pathway is involved in deoxyribonucleic acid (DNA) damage response (DDR), which is crucial to cancer cell survival after treatment with DNA damage agents, including cisplatin (CDDP). Here, we explored the interactions between exonuclease 1 (), a core gene in the HDR pathway, and CDDP resistance in gastric cancer (GC). Using bioinformatics analysis, we identified the HDR pathway as the most amplified pathway in DDR in GC. In addition, was the core gene in the HDR pathway and showed the most significant amplification in GC. The amplification of resulted in higher EXO1 expression in cancerous tissues, with malignant prognostic effects. Moreover, we upregulated or downregulated in GC cells to examine its effects on the cell malignant phenotype and CDDP resistance in vitro and in vivo. The depletion of inhibited cell proliferatory, migratory, and invasive activities, and provided apoptosis resistance to GC cells. expression was elevated in CDDP-resistant cells. Ectopic expression of increased the resistance of GC cells to CDDP, while downregulation of increased the sensitivity of GC cells. Taken together, our study indicates that the HDR pathway is an important player in CDDP resistance in GC through the regulation of .