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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
LncRNA OIP5-AS1 regulates ferroptosis and mitochondrial dysfunction-mediated apoptosis in spinal cord injury by
Zhensong Jiang1, Weimin Zhang1, Jianru Zhang2
1Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Background:
Ferroptosis is an important way of neuronal cell death in acute phase and participates in the inflammatory cascade after spinal cord injury (SCI). It is reported that microRNA (miRNA) and long non-coding RNA (lncRNA) are key mediators in the regulation of ferroptosis. This study will explore the inhibitory effect of LncRNA OIP5-AS1 on ferroptosis and mitochondrial dysfunction-mediated apoptosis in SCI.
Methods:
The ferric ammonium citrate (FAC)-induced cell model and the SCI rat model were established. The expression of LncRNA OIP5-AS1, miR-128-3p and Nrf2 were transfected to evaluated the effect on the viability and apoptosis of FAC-induced cell. The interaction between LncRNA OIP5-AS1 and miR-128-3p or miR-128-3p and Nrf2 were analyzed. In addition, expressions of markers related to ferroptosis and mitochondrial dysfunction were analyzed in vitro and in vivo. Histopathologic slide staining was used to analyze spinal cord injury in vivo.
Results:
LncRNA OIP5-AS1 expression was abnormally down-regulated in FAC-induced SCI cell model and SCI rats. The LncRNA OIP5-AS1 deficiency induced decreased Nrf2 level by less sponging miR-128-3p, thus, aggravating spinal cord injury and inducing more apoptosis, ferroptosis and mitochondrial dysfunction in neural stem cells with SCI. However, overexpression of LncRNA OIP5-AS1 inhibited apoptosis, ferroptosis and mitochondrial dysfunction, thus effectively ameliorating spinal cord injury.
Conclusion:
This finding demonstrates that LncRNA OIP5-AS1 overexpression could enhance the recovery of spinal cord injury by regulating the miR-128-3p/Nrf2 axis.
Insights
Overexpression of LncRNA OIP5-AS1 inhibits ferroptosis and apoptosis, improving spinal cord injury recovery by regulating the miR-128-3p/Nrf2 pathway. This offers a potential therapeutic strategy for neurological damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Death Research
Background:
- Ferroptosis is a key neuronal death pathway in spinal cord injury (SCI) and inflammation.
- MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are critical regulators of ferroptosis.
- LncRNA OIP5-AS1's role in ferroptosis and mitochondrial dysfunction post-SCI requires investigation.
Purpose of the Study:
- To investigate the inhibitory effect of LncRNA OIP5-AS1 on ferroptosis.
- To explore the role of LncRNA OIP5-AS1 in mitochondrial dysfunction-mediated apoptosis in SCI.
- To elucidate the regulatory mechanism involving LncRNA OIP5-AS1, miR-128-3p, and Nrf2 in SCI.
Main Methods:
- Established ferric ammonium citrate (FAC)-induced cell and SCI rat models.
- Analyzed LncRNA OIP5-AS1, miR-128-3p, and Nrf2 expression and interactions.
- Assessed cell viability, apoptosis, ferroptosis, and mitochondrial dysfunction markers in vitro and in vivo.
- Utilized histopathologic slide staining for SCI evaluation.
Main Results:
- LncRNA OIP5-AS1 was downregulated in SCI models.
- LncRNA OIP5-AS1 deficiency exacerbated SCI by reducing Nrf2 via miR-128-3p, increasing apoptosis, ferroptosis, and mitochondrial dysfunction.
- Overexpression of LncRNA OIP5-AS1 ameliorated SCI by inhibiting these detrimental processes.
Conclusions:
- LncRNA OIP5-AS1 overexpression enhances SCI recovery.
- This effect is mediated by regulating the miR-128-3p/Nrf2 axis.
- LncRNA OIP5-AS1 represents a potential therapeutic target for SCI treatment.
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