Silencing of miR20a is crucial for Ngn1-mediated neuroprotection in injured spinal cord

• Published in: Human gene therapy Vol. 23; no. 5; p. 508
• Main Authors: Jee, Min Ki, Jung, Jin Sun, Im, Young Bin, Jung, Sung Jun, Kang, Soo Kyung
• Format: Journal Article
• Language: English
• Published: United States 01.05.2012
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - administration & dosage; Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cell Survival - genetics; Disease Models, Animal; Female; Gene Expression Regulation - genetics; Hindlimb - pathology; Humans; Mice; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; Motor Neurons - metabolism; Motor Neurons - pathology; Myelin Sheath - pathology; Nerve Tissue Proteins - administration & dosage; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - metabolism; RNA Interference; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal Cord Injuries - therapy
• ISSN: 1557-7422
• DOI: 10.1089/hum.2011.121

MicroRNAs (miRNAs) compose a relatively new discipline in biomedical research, and many physiological processes in disease have been associated with changes in miRNA expression. Several studies report that miRNAs participate in biological processes such as the control of secondary injury in several disease models. Recently, we identified novel miRNAs that were abnormally up-regulated in a traumatic spinal cord injury (SCI). In the current study, we focused on miR20a, which causes continuing motor neuron degeneration when overexpressed in SCI lesions. Blocking miR20a in SCI animals led to neural cell survival and eventual neurogenesis with rescued expression of the key target gene, neurogenin 1 (Ngn1). Infusion of siNgn1 resulted in functional deficit in the hindlimbs caused by aggressive secondary injury and actively enhanced the inflammation involved in secondary injury progression. The events involving miR20a underlie motor neuron and myelin destruction and pathophysiology and ultimately block regeneration in injured spinal cords. Inhibition of miR20a expression effectively induced definitive motor neuron survival and neurogenesis, and SCI animals showed improved functional deficit. In this study, we showed that abnormal expression of miR20a induces secondary injury, which suggests that miR20a could be a potential target for therapeutic intervention following SCI.