MicroRNA-410-3p attenuates gemcitabine resistance in pancreatic ductal adenocarcinoma by inhibiting HMGB1-mediated autophagy

Abstract

Gemcitabine-based chemotherapy is the most common treatment option for pancreatic ductal adenocarcinoma (PDAC). However, it offers little therapeutic value in many cases due to the rapid development of chemoresistance. MicroRNAs (miRNAs) have been found to play pivotal roles in the chemotherapeutic resistance of PDAC. We found that miR-410-3p was significantly down-regulated in human pancreatic cancer xenograft (HPCx) tumor tissues from gemcitabine-treated mice. Low miR-410-3p expression correlated with gemcitabine resistance in HPCx tumors and PDAC cells as well as poor prognosis in PDAC patients. We also found that miR-410-3p attenuated the gemcitabine resistance of PDAC by targeting the 3'-UTR of HMGB1. Moreover, our study clearly demonstrated that miR-410-3p enhanced chemosensitivity to gemcitabine via inhibiting HMGB1-induced autophagy during chemotherapy in PDAC cells. Our study suggests that miR-410-3p expression may be a useful indicator of the potential for chemoresistance to gemcitabine and provide a potential new therapeutic target for chemoresistance in PDAC.