Although further studies are needed to fully elucidate the definite regulatory mechanisms of miR-23b-3p, this work suggests the novel miR-23b-3p/ATG12/HMGB2/autophagy-regulatory loop characterized here provides new insight into the mechanisms underlying drug resistance, and restoration of miR-23b-3p expression may be a potential therapeutic strategy for the treatment of MDR in GC. This evidence concerns the gene ATG12 and gastric cancer.