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.

Abstract

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.

• Authors: Jingang Ai, Guolin Tan, Wei Li, Honghui Liu, Tieqi Li, Gehou Zhang, Zheng Zhou, Yu Gan
• Journal: Cell biology and toxicology (Cell Biol Toxicol) Vol. 39 Issue 2 Pg. 537-556 (04 2023) ISSN: 1573-6822 [Electronic] Switzerland
• PMID: 35844005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• Cisplatin
• MicroRNAs
• Sirtuin 1

Topics

• Animals
• Mice
• Nasopharyngeal Carcinoma (genetics, pathology)
• Herpesvirus 4, Human (genetics, metabolism)
• Cisplatin (pharmacology, therapeutic use)
• MicroRNAs (genetics, metabolism)
• Side-Population Cells (metabolism, pathology)
• Exosomes (genetics, metabolism)
• Mice, Nude
• Sirtuin 1 (genetics, metabolism)
• Cell Line, Tumor
• Nasopharyngeal Neoplasms (drug therapy, genetics)
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic