Oncotarget

Research Papers:

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

Junjie Xiong, Dan Wang, Ailin Wei, Nengwen Ke, Yichao Wang, Jie Tang, Sirong He, Weiming Hu and Xubao Liu _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:107500-107512. https://doi.org/10.18632/oncotarget.22494

Metrics: PDF 978 views  |   HTML 2153 views  |   ?  


Abstract

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

Correspondence to:

Xubao Liu, email: liuxb2011@126.com

Keywords: PDAC; miR-410-3p; chemoresistance; HMGB1; autophagy

Received: June 19, 2017     Accepted: October 30, 2017     Published: November 18, 2017

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 22494