Exosomal CircPRRX1 Enhances Doxorubicin Resistance in Gastric Cancer by Regulating MiR-3064-5p/PTPN14 Signaling
10.3349/ymj.2020.61.9.750
- Author:
Shumin WANG
1
;
Mei PING
;
Bin SONG
;
Yarong GUO
;
Yuanfei LI
;
Junmei JIA
Author Information
1. Department of Oncology, First Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province, China.
- Publication Type:Original Article
- From:Yonsei Medical Journal
2020;61(9):750-761
- CountryRepublic of Korea
-
Abstract:
Purpose:Gastric cancer (GC) is a malignant tumor with a high mortality rate. Drug resistance is a major obstacle to GC therapy. This study aimed to investigate the role and mechanism of exosomal circPRRX1 in doxorubicin resistance in GC.
Materials and Methods:HGC-27 and AGS cells were exposed to different doses of doxorubicin to construct doxorubicin-resistant cell lines. Levels of circPRRX1, miR-3064-5p, and nonreceptor tyrosine phosphatase 14 (PTPN14) were detected by quantitative real-time PCR or Western blot assay. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell,and Western blot assays were used to explore the function of circPRRX1 in GC cells. Interactions among circPRRX1, miR-3064-5p,and PTPN14 were confirmed by dual-luciferase reporter assay. The in vivo function of circPRRX1 was analyzed in a xenograft tumor model.
Results:CircPRRX1 was highly expressed in doxorubicin-resistant GC cell lines. Knockdown of circPRRX1 reversed doxorubicin resistance in doxorubicin-resistant GC cells. Additionally, extracellular circPRRX1 was carried by exosomes to spread doxorubicin resistance. CircPRRX1 silencing reduced doxorubicin resistance by targeting miR-3064-5p or regulating PTPN14. In GC patients,high levels of circPRRX1 in serum exosomes were associated with poor responses to doxorubicin treatment. Moreover, depletion of circPRRX1 reduced doxorubicin resistance in vivo.
Conclusion:CircPRRX1 strengthened doxorubicin resistance by modulating miR-3064-5p/PTPN14 signaling and might be a therapeutic target for GC patients.
