载有 circPARD3 的外泌体通过 miR-579-3p/SIRT1/SSRP1 轴促进 EBV-miR-BART4 诱导的鼻咽癌细胞侧群干细胞特性和顺铂耐药性。
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.
机构信息
Department of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.
Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
出版信息
Cell Biol Toxicol. 2023 Apr;39(2):537-556. doi: 10.1007/s10565-022-09738-w. Epub 2022 Jul 18.
OBJECTIVE
To explore the effects of exosomes loaded with circular RNA PARD3 on EBV-miR-BART4-induced stemness 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 stemness and cisplatin resistance in NPC-SP cells, while miR-579-3p reversed the effect of exosomal circPARD3 on EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells. Additionally, miR-579-3p suppressed EBV-miR-BART4-induced stemness 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 stemness and cisplatin resistance in NPC-SP cells.
CONCLUSION
Exosomes loaded with circPARD3 promoted EBV-miR-BART4-induced stemness and cisplatin resistance in NPC-SP cells through the miR-579-3p/SIRT1/SSRP1 axis. Graphical Headlights • EBV-miR-BART4 induces the stemness and resistance of NPC-SP cells. • CircPARD3 regulates SIRT1 by miR-579-3p. • SIRT1 regulates SSRP1 expression by histone methylation. • Exosomes loaded with circPARD3 promotes EBV-miR-BART4-induced NPC-SP cell stemness and resistance by the miR-579-3p/SIRT1/SSRP1 axis.
目的
探讨载环状 RNA PARD3 的外泌体通过 miR-579-3p/SIRT1/SSRP1 轴对 EBV-miR-BART4 诱导的鼻咽癌细胞侧群（NPC-SP）细胞干性和顺铂耐药性的影响。
方法
收集鼻咽癌患者或鼻炎患者的 65 例癌组织和 65 例非癌组织，采用 qRT-PCR、western blot 或免疫组化法检测 circPARD3、miR-579-3p、SIRT1 和 SSRP1 的表达。裸鼠体内肿瘤形成实验。免疫荧光和 qRT-PCR 检测 CD44 和 CD133 表达，流式细胞术联合 Hoechst 33,342 染料外排鉴定 SP 细胞，CCK-8 和 EdU 检测细胞增殖，Transwell 检测迁移和侵袭。
结果
NPC 组织和细胞中 circPARD3、SIRT1 和 SSRP1 表达上调，miR-579-3p 表达下调。CircPARD3 与 SIRT1 和 SSRP1 的表达呈正相关，而 miR-579-3p 与 circPARD3、SIRT1 和 SSRP1 的表达呈负相关。载有 circPARD3 的外泌体促进 EBV-miR-BART4 诱导的 NPC-SP 细胞干性和顺铂耐药性，而 miR-579-3p 逆转了外泌体 circPARD3 对 EBV-miR-BART4 诱导的 NPC-SP 细胞干性和顺铂耐药性的影响。此外，miR-579-3p 通过调控 SIRT1 抑制 EBV-miR-BART4 诱导的 NPC-SP 细胞干性和顺铂耐药性。SIRT1 通过催化 H3K4 甲基化上调 SSRP1 表达，下调 SSRP1 逆转了 SIRT1 对 EBV-miR-BART4 诱导的 NPC-SP 细胞干性和顺铂耐药性的影响。
结论
载 circPARD3 的外泌体通过 miR-579-3p/SIRT1/SSRP1 轴促进 EBV-miR-BART4 诱导的 NPC-SP 细胞干性和顺铂耐药性。
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