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The novel biomarker circ_0020339 drives septic acute kidney injury by targeting miR-17-5p/IPMK axis

  • Nephrology - Original Paper
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Abstract

Purpose

Sepsis is a systemic life-threatening inflammatory disease, which leads to septic acute kidney injury (AKI). Circular RNAs (circRNAs) are involved in septic AKI. Herein, we aimed to expound the action of circ_0020339 in septic AKI. The dysregulation of plasma circRNAs between patients with septic non-AKI and patients with septic AKI were screened by circRNA chip.

Methods

The dysregulation of circ_0020339, microRNA (miR)-17-5p, and inositol polyphosphate multi kinase (IPMK) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. The release of serum creatinine (SCr), tissue inhibitor metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), tumor necrosis factor (TNF)α and interleukin (IL)-1β was evaluated by enzyme-linked immunosorbent assay (ELISA). Bioinformatic analysis, dual-luciferase reporter assay and miRNA pull down assay were used to confirm the interaction between miR-17-5p and circ_0020339 or IPMK 3’untranslated region (UTR). Protein level of IPMK, TNF receptor-associated factor 6 (TRAF6), phosphorylated AKT (p-AKT)/total (t)-AKT, p-nuclear factor kappa-B (NF-κB) kinase (p-IKK)/t-IKK, p-inhibitor of NF-κB (p-IκB)α/t-IκBα, and p-p65/t-p65 were conducted by western blot.

Results

Circ_0020339 was upregulated in the plasma of patients with septic AKI as well as LPS-treated HK2 cells and C57BL/6 mice relative to the corresponding counterparts. Functionally, circ_0020339 was positively correlated with markers of renal functional injury and inflammation in patients with septic AKI; si-circ_0020339 facilitated cell proliferation, while restrained cell apoptosis and inflammation in LPS-triggered HK2 cells; meanwhile, si-circ_0020339 restrained survival rate, renal functional injury and inflammation in LPS-triggered C57BL/6 mice. Furthermore, circ_0020339 and IPMK 3’UTR shared the same complementary sites with miR-17-5p.

Conclusion

si-circ_0020339 attenuated LPS-induced cell damage by targeting miR-17-5p/IPMK axis and inactivation of TRAF6/p-AKT/p-IKK/p-IκBα/p-p65. Altogether, plasma circ_0020339 serves as a novel diagnostic marker of patients with septic AKI.

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They are available from the corresponding author on special request.

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This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Critical Care, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, 830001, Xinjiang, China

    Lu Wang, Boranyi Bayinchahan, Daquan Zhang, Zhigao Wang & Dong Xiao

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  1. Lu Wang
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  2. Boranyi Bayinchahan
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  4. Zhigao Wang
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  5. Dong Xiao
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Contributions

All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript. LW, BB, DZ, and ZW conducted the experiments, DX wrote the manuscript.

Corresponding author

Correspondence to Dong Xiao.

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The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Current study was approved by the Ethics Committee of People’s Hospital of Xinjiang Uygur Autonomous Region.

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Wang, L., Bayinchahan, B., Zhang, D. et al. The novel biomarker circ_0020339 drives septic acute kidney injury by targeting miR-17-5p/IPMK axis. Int Urol Nephrol 55, 437–448 (2023). https://doi.org/10.1007/s11255-022-03331-0

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