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Background <p>Spinal cord injury (SCI) leads to secondary neuronal damage through inflammation and oxidative stress, yet the underlying regulatory mechanisms remain incompletely understood.</p> Methods and Results <p>This study identifies circ-Ttc3 as a protective regulator in SCI-associated neuronal injury using a lipopolysaccharide (LPS)-induced PC12 cell model. circ-Ttc3 expression was significantly downregulated following LPS treatment, while its overexpression restored cell viability, inhibited apoptosis, and suppressed proinflammatory cytokine expression and oxidative stress markers. Mechanistically, bioinformatics and RNA immunoprecipitation (RIP) assays identified RBFOX1 as a direct binding protein of circ-Ttc3. circ-Ttc3 increased RBFOX1 protein levels by enhancing its stability, as shown by cycloheximide chase assays. Functional rescue experiments further revealed that knockdown of RBFOX1 abrogated the protective effects of circ-Ttc3 on inflammation, oxidative stress, and neuronal apoptosis, supporting the existence of a circ-Ttc3/RBFOX1 regulatory axis. These findings demonstrate that circ-Ttc3 mitigates neuronal injury by stabilizing RBFOX1, thereby suppressing secondary injury mechanisms. </p> Conclusions <p>This study highlights a novel circRNA–RNA binding protein (RBP) interaction underlying neuroprotection in LPS-induced oxidative stress and inflammation, and provides new insight into potential therapeutic targets for SCI intervention.</p>

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circ-Ttc3 alleviates LPS-induced neuronal injury via stabilizing RBFOX1 to inhibit inflammation and oxidative stress

  • 期刊论文

  • 发表日期：

    2025年12月28日

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  • Yihui Zhang,
  • Yong Zhu,
  • Qiang Li,
  • Qing Shi,
  • Liang Li

摘要

Background

Spinal cord injury (SCI) leads to secondary neuronal damage through inflammation and oxidative stress, yet the underlying regulatory mechanisms remain incompletely understood.

Methods and Results

This study identifies circ-Ttc3 as a protective regulator in SCI-associated neuronal injury using a lipopolysaccharide (LPS)-induced PC12 cell model. circ-Ttc3 expression was significantly downregulated following LPS treatment, while its overexpression restored cell viability, inhibited apoptosis, and suppressed proinflammatory cytokine expression and oxidative stress markers. Mechanistically, bioinformatics and RNA immunoprecipitation (RIP) assays identified RBFOX1 as a direct binding protein of circ-Ttc3. circ-Ttc3 increased RBFOX1 protein levels by enhancing its stability, as shown by cycloheximide chase assays. Functional rescue experiments further revealed that knockdown of RBFOX1 abrogated the protective effects of circ-Ttc3 on inflammation, oxidative stress, and neuronal apoptosis, supporting the existence of a circ-Ttc3/RBFOX1 regulatory axis. These findings demonstrate that circ-Ttc3 mitigates neuronal injury by stabilizing RBFOX1, thereby suppressing secondary injury mechanisms.

Conclusions

This study highlights a novel circRNA–RNA binding protein (RBP) interaction underlying neuroprotection in LPS-induced oxidative stress and inflammation, and provides new insight into potential therapeutic targets for SCI intervention.