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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

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Cell Biology and Toxicology Aims and scope Submit manuscript

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 abstract

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.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Funding

Thanks for the grants from the National Natural Science Foundations of China to Jingang Ai (No. 81902785) and the Natural Science Foundations of Hunan Province to Jingang Ai (No. 2021JJ40913).

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China

    Jingang Ai, Guolin Tan, Wei Li, Honghui Liu, Tieqi Li, Gehou Zhang & Zheng Zhou

  2. Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Yu Gan

Authors
  1. Jingang Ai
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  2. Guolin Tan
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  3. Wei Li
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  4. Honghui Liu
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  5. Tieqi Li
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  6. Gehou Zhang
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  7. Zheng Zhou
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  8. Yu Gan
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Contributions

AJG and GY conceived the ideas. AJG and GY designed the experiments. AJG and ZZ performed the experiments. AJG and TGL analyzed the data. LW and ZGH provided critical materials. LHH and LTQ wrote the manuscript. AJG supervised the study. All the authors have read and approved the final version for publication.

Corresponding authors

Correspondence to Zheng Zhou or Yu Gan.

Ethics declarations

Ethics approval and consent to participate

Informed written consent from the patients and approval from the Ethics Committee of The Third Xiangya Hospital had been obtained before the collection of clinical tissues. Animal experiments were approved by the Animal Research Ethics Committee of The Third Xiangya Hospital and performed per the guidelines of the Ministry of Science and Technology of the People's Republic of China.

Consent for publication

Informed written consent from the patients and approval from the Ethics Committee of The Third Xiangya Hospital had been obtained before the collection of clinical tissues.

Conflicts of interest

The authors declare no competing interests.

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Ai, J., Tan, G., Li, W. et al. 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 Biol Toxicol 39, 537–556 (2023). https://doi.org/10.1007/s10565-022-09738-w

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  • DOI: https://doi.org/10.1007/s10565-022-09738-w

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