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Updated: Dec 25, 2025
Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury
Published on: February 23, 2015
A circRNA derived from linear HIPK3 relieves the neuronal cell apoptosis in spinal cord injury via ceRNA pattern
Jingwei Zhao1, Xi Qi1, Jingyu Bai2
1Division of Spine Surgery, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Insights
Circular RNA HIPK3 (circ-HIPK3) reduces neuronal cell apoptosis in spinal cord injury (SCI). It functions by regulating the miR-558/DPYSL5 axis, offering a potential therapeutic target for SCI.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Spinal cord injury (SCI) is a debilitating condition with significant health implications.
- Circular RNAs (circRNAs) are emerging as key regulators of cellular processes, including neuronal function.
- The specific role of circ-HIPK3 in the context of SCI remains largely unexplored.
Purpose of the Study:
- To investigate the mechanism by which circ-HIPK3 influences neuronal cell function in spinal cord injury.
- To elucidate the role of circ-HIPK3 in regulating neuronal apoptosis following SCI.
Main Methods:
- Construction of an in vivo rat model of spinal cord injury.
- Establishment of an in vitro SCI model using AGE1.HN and PC12 cells treated with CoCl2.
- Assessment of neuronal apoptosis using functional assays, RNase R, and Actinomycin D treatments.
- Analysis of the regulatory axis involving circ-HIPK3, miR-558, and DPYSL5.
Main Results:
- Circ-HIPK3 expression was found to be downregulated in both in vivo SCI models and in vitro SCI cell models.
- Inhibition of circ-HIPK3 exacerbated neuronal apoptosis, while its overexpression reduced apoptosis.
- Circ-HIPK3 acts as a competing endogenous RNA (ceRNA) for miR-558, thereby upregulating DPYSL5 expression.
- The circ-HIPK3/miR-558/DPYSL5 axis was confirmed to modulate neuronal apoptosis in SCI.
Conclusions:
- Circ-HIPK3 plays a protective role against neuronal cell apoptosis in spinal cord injury.
- The protective effect is mediated through the circ-HIPK3/miR-558/DPYSL5 regulatory pathway.
- Circ-HIPK3 represents a potential therapeutic target for mitigating neuronal damage in SCI.
Abstract:
Spinal cord injury (SCI) is a severe disable symptom and has posed a great health threat to many people. Circ-HIPK3 has been reported to modulate the biological behavior of neuronal cells. Thence, in this study, we explored the mechanism of circ-HIPK3 in affecting functions of neuronal cell in SCI. SCI rat model was constructed to evaluate the apoptosis condition of spinal cord tissue. Meanwhile, 100 μM of CoCl2 was used to treat AGE1.HN and PC12 cells to induce in vitro SCI model. Functional assays were implemented to investigate the apoptosis of AGE1.HN and PC12 cells. RNase R and Act D treatment were both conducted to verify the circular character of circ-HIPK3. In this study, circ-HIPK3 was found lowly expressed in SCI rat models and AGE1.HN and PC12 cells induced by 100uM of CoCl2. Meanwhile, inhibited circ-HIPK3 or overexpressed circ-HIPK3 could separately elevate or reduce the apoptosis of AGE1.HN and PC12 cells. Moreover, circ-HIPK3 was identified as the ceRNA against miR-558 to up-regulate DPYSL5. Circ-HIPK3/miR-558/DPYSL5 axis modulated the apoptosis of AGE1.HN and PC12 cells in SCI. In conclusion, circ-HIPK3 relieves the neuronal cell apoptosis through regulating miR-588/DPYSL5 axis in SCI.
