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LncRNA-SNHG3 promotes neuroinflammation post-intracerebral hemorrhage by regulating the miR-106b-5p/TXNIP axis

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Abstract

Background

Intracerebral hemorrhage (ICH) stands as the most fatal stroke subtype, lacking any specific therapeutic approach yielding benefits for functional recovery.

Objectives

We aimed to explore the involvement of long non-coding RNA small nucleolar RNA host gene 3 (lncRNA-SNHG3) in post-ICH neuroinflammation, offering a novel rationale for ICH treatment.

Results

Brain tissues of ICH-induced mice exhibited upregulated levels of lncRNA-SNHG3. Inhibition of lncRNA-SNHG3 led to reduced modified neurological severity scores, diminished brain edema, and attenuated inflammatory infiltration, coupled with reduced levels of tumor necrosis factor-α/interleukin-1β. By repressing miR-106b-5p via targeted binding, lncRNA-SNHG3 facilitated the inhibition of transcriptional and protein levels of thioredoxin-interacting protein (TXNIP) through targeted binding to TXNIP mRNA. The counteraction of miR-106b-5p inhibition or the upregulation of TXNIP reversed the ameliorative effect of sh-SNHG3 on neuroinflammation.

Conclusion

Competitive binding of lncRNA-SNHG3 to miR-106b-5p resulted in the upregulation of TXNIP, consequently inducing neuroinflammation and exacerbating ICH-induced damage.

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Data availability

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

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Acknowledgements

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, People’s Republic of China

    Fenggang Zhou

  2. Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, People’s Republic of China

    Fei Wu, Xinran Wang, Shihua Yu, Wenqi Tian & Ou Lv

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  1. Fenggang Zhou
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  6. Ou Lv
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Contributions

Guarantor of integrity of the entire study: OL; study concepts: OL; study design: OL; definition of intellectual content: FZ; literature research: FZ; clinical studies: FW; experimental studies: FW; data acquisition: XW; data analysis: SY; statistical analysis: SY; manuscript preparation: WT; manuscript editing: WT; manuscript review: OL.

Corresponding author

Correspondence to Ou Lv.

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Conflict of interest

Fenggang Zhou, Fei Wu, Xinran Wang, Shihua Yu, Wenqi Tian, Ou Lv declare that there is no conflict of interest.

Ethical approval

All procedures got the approval of the Animal Research Ethics Committee of The Second Affiliated Hospital of Harbin Medical University and followed the Guide for the Care and Use of Laboratory Animals [National Academies Press (US) 2011].

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Zhou, F., Wu, F., Wang, X. et al. LncRNA-SNHG3 promotes neuroinflammation post-intracerebral hemorrhage by regulating the miR-106b-5p/TXNIP axis. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00397-4

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