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Circ_0101874 overexpression strengthens PDE4D expression by targeting miR-335-5p to promote neuronal injury in ischemic stroke

  • Author Footnotes
    1 These authors contributed equally to this work.
    Liangyan Pei
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Neurology, The First People's Hospital of Jingmen, No.168 Xiangshan Avenue, Duodao District, Jingmen, Hubei 448000, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Xiaofan Xu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Stomatology, Jingmen Rehabilitation Hospital, China
    Search for articles by this author
  • Tianqi Yuan
    Correspondence
    Corresponding author.
    Affiliations
    Department of Neurology, The First People's Hospital of Jingmen, No.168 Xiangshan Avenue, Duodao District, Jingmen, Hubei 448000, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Abstract

      Background

      Ischemic stroke has been a public concern, while its pathogenesis is not fully understood. Increasing evidence suggests that circular RNAs (circRNAs) are involved in this disorder. The purpose of this study was to explore the role of circ_0101874 in ischemic stroke.

      Methods

      The in vivo model of ischemic stroke was established in mice with middle cerebral artery occlusion (MCAO) treatment. The in vitro model of ischemic stroke was established in SK-N-SH cells with oxygen-glucose deprivation (OGD) treatment. The expression of circ_0101874, miR-335-5p and phosphodiesterase 4D (PDE4D) mRNA was measured by quantitative real-time PCR (qPCR). The release of inflammatory factors was checked by ELISA. Cell viability, cell proliferation and cell apoptosis were detected using CCK-8 assay, EdU assay and flow cytometry assay, respectively. The protein levels of cyclinD1, cleaved-caspase-3 and PDE4D were detected by western blot. The interaction between miR-335-5p and circ_0101874 or PDE4D was validated by dual-luciferase reporter assay and RIP assay.

      Results

      Circ_0101874 was highly expressed in MCAO animal models and OGD-induced SK-N-SH cells. Circ_0101874 knockdown suppressed OGD-enhanced inflammation, cell apoptosis and oxidative stress and promoted OGD-inhibited cell viability and cell proliferation in SK-N-SH cells. Circ_0101874 directly bound to miR-335-5p, and miR-335-5p inhibition reversed the effects of circ_0101874 knockdown. PDE4D was a target gene of miR-335-5p, and PDE4D overexpression recovered OGD-promoted SK-N-SH cell injuries that were blocked by miR-335-5p enrichment. Circ_0101874 bound to miR-335-5p to enhance the expression of PDE4D.

      Conclusion

      Circ_0101874 knockdown alleviated OGD-induced neuronal cell injury by suppressing PDE4D via regulating miR-335-5p.

      Keywords

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