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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
Cell Biology and Toxicology ( IF 6.1 ) Pub Date : 2022-07-18 , DOI: 10.1007/s10565-022-09738-w
Jingang Ai 1 , Guolin Tan 1 , Wei Li 1 , Honghui Liu 1 , Tieqi Li 1 , Gehou Zhang 1 , Zheng Zhou 1 , Yu Gan 2
Affiliation  

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 abstract



中文翻译:

载有 circPARD3 的外泌体通过 miR-579-3p/SIRT1/SSRP1 轴促进鼻咽癌侧群细胞中 EBV-miR-BART4 诱导的干性和顺铂耐药性

客观的

通过 miR-579-3p/SIRT1/SSRP1 轴探索装载环状 RNA PARD3 的外泌体对 EBV-miR-BART4 诱导的鼻咽癌侧群 (NPC-SP) 细胞干性和顺铂耐药性的影响。

方法

从 NPC 患者或鼻炎患者中收集了 65 个癌组织和 65 个非癌组织。通过 qRT-PCR、western blot 或免疫组化检测 circPARD3、miR-579-3p、SIRT1 和 SSRP1 的表达。在裸鼠中进行体内肿瘤形成测定。免疫荧光和 qRT-PCR 用于测定 CD44 和 CD133 表达,流式细胞术结合 Hoechst 33,342 染料流出鉴定 SP 细胞,CCK-8 和 EdU 测定细胞增殖,Transwell 测定迁移和侵袭。

结果

CircPARD3、SIRT1 和 SSRP1 在 NPC 组织和细胞中被上调,而 miR-579-3p 被下调。CircPARD3与SIRT1、SSRP1的表达呈正相关,miR-579-3p与circPARD3、SIRT1、SSRP1呈负相关。装载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逆转外泌体circPARD3对EBV-miR-BART4诱导的NPC-SP干性和顺铂耐药性的影响细胞。此外,miR-579-3p 通过调节 SIRT1 抑制 NPC-SP 细胞中 EBV-miR-BART4 诱导的干性和顺铂耐药性。SIRT1 通过催化 H3K4 甲基化上调 SSRP1 表达,下调 SSRP1 逆转 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

载有 circPARD3 的外泌体通过 miR-579-3p/SIRT1/SSRP1 轴促进 NPC-SP 细胞中 EBV-miR-BART4 诱导的干性和顺铂耐药性。

图形概要

更新日期:2022-07-19
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