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



      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.


      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.


      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.


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


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