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  4. Cooperation of long noncoding RNA LOC100909675 and transcriptional regulator CTCF modulates Cdk1 transcript to control astrocyte proliferation

Cooperation of long noncoding RNA LOC100909675 and transcriptional regulator CTCF modulates Cdk1 transcript to control astrocyte proliferation

J. Biol. Chem., 2023 · DOI: https://doi.org/10.1016/j.jbc.2023.105153 · Published: August 9, 2023

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

Astrocyte activation and proliferation contribute to glial scar formation during spinal cord injury (SCI), which limits nerve regeneration. Long noncoding RNAs (lncRNAs) are involved in astrocyte proliferation and act as novel epigenetic regulators. The study found that lncRNA-LOC100909675 (LOC9675) expression increased after SCI, and reducing its expression decreased the proliferation and migration of spinal astrocytes. Depleting LOC9675 reduced astrocyte proliferation and facilitated axonal regrowth after SCI. The study suggests that cooperation between CTCF and LOC9675 regulates Cdk1 transcription, thereby controlling astrocyte proliferation. This provides a novel perspective on Cdk1 gene transcript regulation by lncRNA LOC9675.

Study Duration
56 days
Participants
Sprague-Dawley rats, primary cultured spinal neurons and astrocytes
Evidence Level
Not specified

Key Findings

  • 1
    LOC9675 expression promptly increased after SCI, and reducing its expression decreased the proliferation and migration of cultured spinal astrocytes.
  • 2
    LOC9675 directly interacted with the transcriptional regulator CCCTC-binding factor (CTCF), which is a novel regulator of the Cdk1 gene.
  • 3
    Simultaneous overexpression of CTCF and LOC9675 in astrocytes restored the Cdk1 transcript to the normal level.

Research Summary

This study investigates the role of lncRNA LOC100909675 (LOC9675) in astrocyte proliferation following spinal cord injury (SCI). It finds that LOC9675 expression increases after SCI and promotes astrocyte proliferation and migration. The study identifies that LOC9675 interacts with the transcriptional regulator CTCF, and this interaction modulates the expression of Cdk1, a key regulator of the cell cycle. The findings suggest that LOC9675 stabilizes Cdk1 mRNA and increases CDK1 protein, thus contributing to cell proliferation. The interaction of CTCF-LOC9675 undocks LOC9675 from Cdk1 mRNA, thus maintaining Cdk1 mRNA at a normal level.

Practical Implications

Therapeutic Target for SCI

Targeting LOC9675 or its interaction with CTCF could offer a novel therapeutic strategy to reduce glial scar formation and promote axonal regeneration after SCI.

Understanding Cdk1 Regulation

The study provides new insights into the complex regulation of Cdk1, a critical cell cycle regulator, particularly in the context of astrocyte proliferation.

LncRNA Function in CNS

The research highlights the important role of lncRNAs in regulating gene expression and cellular processes in the central nervous system, particularly in response to injury.

Study Limitations

  • 1
    The study primarily focuses on the rat model of SCI, and further research is needed to validate these findings in humans.
  • 2
    The exact mechanisms by which LOC9675 stabilizes Cdk1 mRNA require further investigation.
  • 3
    The study does not explore the potential off-target effects of LOC9675 depletion or CTCF modulation.

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