Long noncoding RNA ZFAS1 aggravates spinal cord injury by binding with miR-1953 and regulating the PTEN/PI3K/AKT pathway.

Abstract

Multiple evidence has shown that long non-coding RNAs (lncRNAs) are novel modulators in the development of many neurological diseases, including spinal cord injury (SCI). Recently, a novel lncRNA zinc finger antisense 1 (ZFAS1) has been found to facilitate the development of many human diseases. However, the effect of ZFAS1 in SCI has not been explored. In the present study, we used the SCI mouse models and LPS-treated BV-2 cellular models to explore the role of ZFAS1 in SCI. Basso Mouse Scale score was applied to reveal locomotor function. Cresyl violet staining was used to reveal volume of spared myelin around the lesion in the injured cord. RIP and luciferase reporter assay were applied to detect binding capacity among RNAs. Next, ZFAS1 was identified to be upregulated in spinal cord tissues of SCI mice. ZFAS1 knockdown promoted functional recovery and inhibited cell apoptosis and the inflammatory response in SCI mice. ZFAS1 bound with microRNA 1953 (miR-1953), and miR-1953 was downregulated in spinal cord tissues of SCI mice. Furthermore, we confirmed that ZFAS1 promoted SCI progression via binding with miR-1953. In addition, phosphatase and tensin homolog (PTEN) was verified to be a downstream target for miR-1953 in vitro, and PTEN was upregulated in spinal cord tissues of SCI mice. Finally, we illustrated that ZFAS1 inactivated the PI3K/AKT pathway through upregulation of PTEN. In conclusion, our study revealed that ZFAS1 facilitated SCI by binding with miR-1953 and regulating the PTEN/PI3K/AKT pathway, which may provide a potential novel insight for treatment of SCI.

• Authors: Yunxiang Chen, Zijian Wei, Jun Liu, Hao Xie, Binbin Wang, Ji Wu, Zezhang Zhu, Yuejun Fan
• Journal: Neurochemistry international (Neurochem Int) Vol. 147 Pg. 104977 (07 2021) ISSN: 1872-9754 [Electronic] England
• PMID: 33524472 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• MicroRNAs
• RNA, Long Noncoding
• Proto-Oncogene Proteins c-akt
• Zinc

Topics

• Animals
• Apoptosis (genetics, physiology)
• Cell Proliferation (genetics)
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Long Noncoding (genetics)
• Recovery of Function (genetics, physiology)
• Spinal Cord (metabolism)
• Spinal Cord Injuries (genetics, metabolism)
• Zinc (metabolism)
• Mice