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

## TL;DR

This study discovers a new RNA called AGAPIR that helps improve blood flow and motor function after spinal cord surgery for a common spinal disorder.

## Contribution

AGAPIR is a novel piRNA that enhances post-decompression angiogenesis and motor recovery in DCM through the USP18/HIF-1α pathway.

## Key findings

- AGAPIR is significantly upregulated in the spinal cord after surgical decompression and correlates with improved angiogenesis.
- Overexpression of AGAPIR promotes blood vessel formation and motor function recovery in DCM mice.
- AGAPIR interacts with USP18 to stabilize HIF-1α, enhancing its deubiquitinating activity and angiogenesis.

## Abstract

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction worldwide. Although surgical decompression can halt disease progression and improve neurological function in most patients, there remains a subset for whom functional improvement is limited. Impaired spinal cord perfusion is a pathological hallmark of DCM, which highlights the importance of restoring blood flow to enhance neurological outcomes. Here, this work identifies a novel angiogenesis‐associated PIWI‐interacting RNA (AGAPIR) that enhances angiogenesis and motor function following spinal cord decompression. Using piRNA sequencing, this work identifies AGAPIR as a key regulator of DCM pathogenesis. This work observes significant upregulation of AGAPIR expression in the spinal cord following surgical decompression, which is correlated with enhanced angiogenesis. Overexpression of AGAPIR markedly improves blood vessel formation and promotes motor function in mice following spinal cord decompression. Using RNA sequencing and cellular validation, this work finds that AGAPIR directly interacts with USP18, leading to an increase in its protein expression level and stabilization of HIF‐1α protein via its deubiquitinating activity. This data demonstrate that AGAPIR is a novel piRNA that further improves the functional status of DCM mice following surgical decompression. These results provide the pioneering evidence and novel insights into piRNA‐directed therapeutic strategies for DCM.

The restoration of blood flow following surgical decompression for degenerative cervical myelopathy (DCM) significantly contributes to the amelioration of neurological deficits. This study identifies AGAPIR, an angiogenesis‐associated PIWI‐interacting RNA, enhances angiogenesis and motor function recovery post‐spinal cord decompression in a mouse model of DCM. Mechanistically, AGAPIR facilitates angiogenesis through the modulation of the USP18/HIF‐1α axis.