EGFR upregulates miRNA subset to inhibit CYBRD1 and cause DDP resistance in gastric cancer

Abstract

Chemoresistance is a considerable challenge for gastric cancer (GC), and the combination of cisplatin (DDP) and anti-EGFR therapy failed to show remarkable benefit. So other targets in EGFR-overexpressed and DDP-resistant GC need to be explored. Both cytological experiments and database bioinformatics analysis were applied in this study. It was confirmed that the prognosis of GC patients with EGFR oe was poor. EGFR regulated intracellular redox metabolism, enhanced GSH content and led to DDP resistance. A subset of miRNAs including miR-135b, miR-106a, miR-29a, miR-23a and miR-15a was upregulated in EGFR-overexpressed and DDP-resistant GC cells. Furthermore, EGFR inhibited CYBRD1 via enhancing the miRNA subset and scavenged the redundant ROS to cause DDP resistance. Therefore, to inhibit the miRNA subset at the same time of anti-EGFR therapy might reverse DDP resistance, serving as a potential novel drug for the future treatment of EGFR-overexpressed and DDP-resistant GC.