AGAPIR: A Novel PIWI-Interacting RNA Enhancing Post-Decompression Angiogenesis in Degenerative Cervical Myelopathy

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Degenerative cervical myelopathy (DCM) is a leading cause of spinal cord dysfunction globally.
• While surgery can halt progression, some patients experience limited functional recovery.
• Impaired spinal cord perfusion is a key pathology in DCM, necessitating strategies to improve blood flow.

Purpose of the Study:

• To identify novel molecular targets for enhancing recovery after DCM surgery.
• To investigate the role of PIWI-interacting RNAs (piRNAs) in DCM pathogenesis and recovery.
• To explore AGAPIR as a potential therapeutic agent for improving angiogenesis and motor function in DCM.

Main Methods:

• piRNA sequencing to identify key regulatory RNAs in DCM.
• RNA sequencing and cellular assays to elucidate molecular mechanisms.
• In vivo studies in mouse models of DCM to assess functional and angiogenic outcomes.

Main Results:

• AGAPIR, an angiogenesis-associated piRNA, was identified as a key regulator in DCM.
• AGAPIR expression is upregulated post-decompression surgery and correlates with enhanced angiogenesis.
• AGAPIR overexpression improved blood vessel formation and motor function in DCM mice by stabilizing HIF-1α via USP18 interaction.

Conclusions:

• AGAPIR is a novel piRNA that promotes angiogenesis and improves motor function in DCM.
• AGAPIR enhances functional recovery by increasing USP18 protein levels and stabilizing HIF-1α.
• These findings introduce piRNA-based therapeutic strategies for managing DCM and improving patient outcomes.