Long non-coding RNA GAS5 promotes neuronal apoptosis in spinal cord injury via the miR-21/PTEN axis
Year: 2025
Type: article
Abstract: BACKGROUND Spinal cord injury (SCI) is a severe and permanent trauma that often leads to significant motor, sensory, and autonomic dysfunction. Neuronal apoptosis is a major pathomechanism underlying secondary injury in SCI. Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression and cellular processes, including apoptosis. However, the role of lncRNA growth arrest-specific transcript 5 (GAS5) in SCI-induced neuronal apoptosis remains unclear. AIM To investigate the role of lncRNA GAS5 in SCI-induced neuronal apoptosis via its interaction with microRNA (miR)-21 and the phosphatase and tensin homolog (PTEN)/AKT pathway. METHODS SCI rat models and hypoxic neuronal cell models were established. Motor function was assessed using the Basso-Beattie-Bresnahan score. Expression levels of GAS5, miR-21, PTEN, caspase 3, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and AKT were measured using quantitative PCR or Western blot analysis. Neuronal apoptosis was determined by TUNEL staining. Dual-luciferase reporter assays validated GAS5-miR-21 binding. Knockdown and overexpression experiments explored the functional effects of the GAS5/miR-21 axis. RESULTS GAS5 was significantly upregulated in the spinal cord following SCI, coinciding with increased neuronal apoptosis and decreased AKT activation. In vitro experiments demonstrated that GAS5 acted as a molecular sponge for miR-21, leading to increased PTEN expression and inhibition of the AKT signaling pathway, thereby promoting apoptosis. In vivo , GAS5 knockdown attenuated neuronal apoptosis, enhanced AKT activation, and improved motor function recovery in SCI rats. CONCLUSION GAS5 promotes neuronal apoptosis in SCI by binding to miR-21 and upregulating PTEN expression, inhibiting the AKT pathway. Targeting GAS5 may represent a novel therapeutic strategy for SCI.
Source: World Journal of Orthopedics
Authors: Ying-Jie Wang, Zhong-Zheng Zhi, Tao Liu, Jian Kang, Guang-Hui Xu
Language: English
Topic: Spinal Cord Injury Research
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4410386259