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CircHIPK3 Promotes Gemcitabine (GEM) Resistance in Pancreatic Cancer Cells by Sponging miR-330-5p and Targets RASSF1

Authors Liu Y, Xia L, Dong L, Wang J, Xiao Q, Yu X, Zhu H

Received 20 November 2019

Accepted for publication 6 January 2020

Published 11 February 2020 Volume 2020:12 Pages 921—929

DOI https://doi.org/10.2147/CMAR.S239326

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Yunfei Liu, 1 Li Xia, 2 Luo Dong, 1 Jiale Wang, 1 Qiangsheng Xiao, 1 Xiao Yu, 1 Hongwei Zhu 3

1Department of Hepatobiliary and Pancreatic Surgery‖, Third Xiangya Hospital, Central South University, Changsha 410006, People’s Republic of China; 2Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, 410006, People’s Republic of China; 3Department of Gastroenterology and Hepatology, Third Xiangya Hospital, Central South University, Changsha, 410006, People’s Republic of China

Correspondence: Xiao Yu
Department of Hepatobiliary and Pancreatic Surgery‖, Third Xiangya Hospital, Central South University, Changsha 410006, People’s Republic of China
Tel/Fax +86 731-88618831
Email lyfxys@sina.com

Hongwei Zhu
Department of Gastroenterology and Hepatology, Third Xiangya Hospital, Central South University, Changsha, 410006, Republic of China
Tel/Fax +86 731-88618831
Email wsqjms123456@163.com

Background: Pancreatic cancer is one of the most common malignant diseases in the world. Gemcitabine chemotherapy remains the most important clinical treatment. However, research found that pancreatic cancer cells have chemoresistance to gemcitabine and the effect is not satisfactory. Therefore, it is urgent to find an effective early diagnosis and treatment strategy. Circular RNA is one of the most popular prognostic biomarkers in GEM-resistant PC.
Materials and Methods: The present study was designed to evaluate the role of circHIPK3 in PC. The expression of circHIPK3 in PC tissues and cells and its effect on proliferation, migration, invasion, EMT, and apoptosis were investigated in vitro; its effect on tumor xenografts was assessed in vivo. Used bioinformation analysis to predict which miRNAs could potentially interact with circHIPK3, mRNA, and miR-330-5p.
Results: RT-PCR showed that the level of circHIPK3 was increased in PC tumor tissues; moreover, circHIPK3 was also increased in GEM-resistant PC tumors tissues and GEM-resistant PC cells. Sh-circHIPK3 could knockdown circHIPK3 in PANC-1-GEM and SW-1990-GEM and could significantly inhibit cell proliferation, invasion, migration, EMT and enhance cell apoptosis, compare with control group, the tumor xenografts of circHIPK3 knockdown group were significantly smaller. CircHIPK3 served as a sponge for miR-330-5p, and miR-330-5p directly bound to the 3′ UTR of RASSF1 were revealed by dual luciferase assay and RIP in PC cells. CircHIPK3 knockdown of RASSF1 expression could neutralize the cytological function of PC cells by miR-330-5p inhibitor mediated GEM-resistance.
Conclusion: CircHIPK3 promote gemcitabine (GEM) resistance in pancreatic cancer cells by targeting RASSF1 via miR-330-5p and regulates proliferation, invasive, migration, EMT, and apoptosis. Our research revealed that circHIPK3 may be a novel biomarker in GEM-resistant PC and could be used as a prognostic target.

Keywords: pancreatic cancer, circular RNA, gemcitabine resistance, biomarker

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