MicroRNA-410-3p attenuates gemcitabine resistance in pancreatic ductal adenocarcinoma by inhibiting HMGB1-mediated autophagy
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Junjie Xiong1,*, Dan Wang2,*, Ailin Wei1,3, Nengwen Ke1, Yichao Wang4, Jie Tang5, Sirong He6, Weiming Hu1 and Xubao Liu1
1Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
2Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China
3Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China
4Department of Thyroid Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
5State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
6Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
*These authors contributed equally to this work
Xubao Liu, email: firstname.lastname@example.org
Keywords: PDAC; miR-410-3p; chemoresistance; HMGB1; autophagy
Received: June 19, 2017 Accepted: October 30, 2017 Published: November 18, 2017
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.
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