Exosomes loaded with circPARD3 promotes EBV-miR-BART4-induced stemness and cisplatin resistance in nasopharyngeal carcinoma side population cells through the miR-579-3p/SIRT1/SSRP1 axis

被引:18
作者
Ai, Jingang [1 ]
Tan, Guolin [1 ]
Li, Wei [1 ]
Liu, Honghui [1 ]
Li, Tieqi [1 ]
Zhang, Gehou [1 ]
Zhou, Zheng [1 ]
Gan, Yu [2 ]
机构
[1] Cent South Univ, Xiangya Hosp 3, Dept Otolaryngol Head & Neck Surg, Changsha 410013, Hunan, Peoples R China
[2] Cent South Univ, Xiangya Hosp, Dept Urol, Changsha 410008, Hunan, Peoples R China
关键词
Circular RNA PARD3; MicroRNA-579-3p/SIRT1/SSRP1; axis; EBV-miR-BART4; Sternness; Cisplatin resistance; INHIBITS PROLIFERATION; SIRT1; CANCER; MIR-579-3P;
D O I
10.1007/s10565-022-09738-w
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objective To explore the effects of exosomes loaded with circular RNA PARD3 on EBV-miR-BART4-induced sternness and resistance of cisplatin in nasopharyngeal carcinoma side population (NPC-SP) cells through the miR-579-3p/SIRT1/SSRP1 axis. Methods Sixty-five cancer tissues and 65 noncancerous tissues were collected from NPC patients or patients with rhinitis. The expressions of circPARD3, miR-579-3p, SIRT1, and SSRP1 were detected by qRT-PCR, western blot, or immunohistochemistry. In vivo tumor formation assay was performed in nude mice. Immunofluorescence and qRT-PCR were conducted for the determination of CD44 and CD133 expressions, and flow cytometry combined with Hoechst 33,342 dye efflux for identifying SP cells, CCK-8 and EdU assays for cell proliferation, and Transwell assay for migration and invasion. Results CircPARD3, SIRT1, and SSRP1 were upregulated while miR-579-3p was downregulated in NPC tissues and cells. CircPARD3 was positively correlated with the expressions of SIRT1 and SSRP1, and miR-579-3p was negatively correlated with circPARD3, SIRT1, and SSRP1. Exosomes loaded with circPARD3 promoted EBV-miR-BART4-induced sternness and cisplatin resistance in NPC-SP cells, while miR-579-3p reversed the effect of exosomal circPARD3 on EBV-miR-BART4-induced sternness and cisplatin resistance in NPC-SP cells. Additionally, miR-579-3p suppressed EBV-miR-BART4-induced sternness and cisplatin resistance in NPC-SP cells by regulating SIRT1. SIRT1 upregulated SSRP1 expression by catalyzing H3K4 methylation and down-regulation of SSRP1 reversed the effect of SIRT1 on EBV-miR-BART4-induced sternness and cisplatin resistance in NPC-SP cells. Conclusion Exosomes loaded with circPARD3 promoted EBV-miR-BART4-induced sternness and cisplatin resistance in NPC-SP cells through the miR-579-3p/SIRT1/SSRP1 axis.
引用
收藏
页码:537 / 556
页数:20
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