Overexpression of long noncoding RNA colorectal neoplasia differentially expressed protects spinal cords against ischemia by targeting microRNA-181a-5p/Sirtuin-1 axis.

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.