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Overexpression of long noncoding RNA colorectal neoplasia differentially expressed protects spinal cords against
Zhi Wang1,2, Wei Wang1,3, Rui Tang1
1Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
Objective:
The objective of this study was to investigate the neuroprotective effects of long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) on ischemic spinal cords.
Materials And Methods:
The binding relationship between CRNDE and microRNA-181a-5p was detected using dual luciferase assays. Spinal cord ischemia was induced in rats by cross clamping the descending aorta. CRNDE expression was induced by intrathecal injection of adeno-associated virus vectors containing CRNDE. The hind-limb motor function of the rats was then assessed over a period of 3 weeks following reperfusion. Lumbar spinal cords were harvested for histologic examinations. Expressions of CRNDE, microRNA-181a-5p and related proteins were measured by quantitative reverse transcription polymerase chain reaction and Western blot.
Results:
Luciferase assays demonstrated that CRNDE bound to microRNA-181a-5p, and Sirt1 was a direct target of microRNA-181a-5p. The transient ischemia induced a significant decrease of CRNDE expression accompanied by a robust increase of microRNA-181a-5p expression in spinal cords. Intrathecal injection of adeno-associated virus vectors containing CRNDE resulted in a significant enhancement of CRNDE expression and a repression of microRNA-181a-5p expression in spinal cords. Consequently, CRNDE overexpression was found to inhibit neuronal apoptosis, attenuate histologic damage, increase the number of surviving neurons, and improve the hind-limb motor function after spinal cord ischemia.
Conclusion:
CRNDE overexpression induces spinal cord protection against ischemia-reperfusion injury, possibly via microRNA-181a-5p/Sirt1 axis.
Insights
Long non-coding RNA CRNDE protects spinal cords from ischemia-reperfusion injury. CRNDE overexpression improves motor function and reduces neuronal damage by targeting the microRNA-181a-5p/Sirt1 pathway.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Spinal cord ischemia-reperfusion injury (SCIRI) causes significant neurological deficits.
- Long non-coding RNAs (lncRNAs) play crucial roles in cellular responses to injury.
- Colorectal neoplasia differentially expressed (CRNDE) is an lncRNA with potential regulatory functions.
Purpose of the Study:
- To investigate the neuroprotective effects of CRNDE in a rat model of SCIRI.
- To elucidate the molecular mechanism underlying CRNDE's action, focusing on its interaction with microRNA-181a-5p (miRNA-181a-5p).
Main Methods:
- Establishment of a rat model of SCIRI.
- Intrathecal administration of adeno-associated virus vectors to modulate CRNDE expression.
- Dual luciferase assays to confirm the binding relationship between CRNDE and miRNA-181a-5p.
- Assessment of motor function, histological damage, neuronal survival, and molecular marker expression (CRNDE, miRNA-181a-5p, Sirt1).
Main Results:
- CRNDE directly binds to miRNA-181a-5p, and Sirt1 is a target of miRNA-181a-5p.
- Ischemia significantly decreased CRNDE and increased miRNA-181a-5p expression in spinal cords.
- CRNDE overexpression attenuated neuronal apoptosis, reduced histological damage, increased neuron survival, and improved motor function post-ischemia.
- CRNDE overexpression led to decreased miRNA-181a-5p expression.
Conclusions:
- CRNDE exhibits significant neuroprotective effects against SCIRI in rats.
- The protective mechanism involves the CRNDE/miRNA-181a-5p/Sirt1 axis.
- CRNDE represents a potential therapeutic target for managing spinal cord ischemia-reperfusion injury.
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