Long Non-coding RNA RMST Worsens Ischemic Stroke via MicroRNA-221-3p/PIK3R1/TGF-beta Signaling Pathway

Much efforts have been made to probe the mechanism underlying ischemic stroke (IS). This study was proposed to uncover the role of long non-coding RNA rhabdomyosarcoma 2 related transcript (RMST) in IS through microRNA-221-3p (miR-221-3p)/phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1)/transforming growth factor-beta (TGF-beta) axis. Neurological behavioral function, pathological changes in brain tissue, oxidative stress, and inflammation responses in middle cerebral artery occlusion (MCAO) mice were tested. RMST, miR-221-3p, PIK3R1, and TGF-beta signaling-related protein expression in brain tissues of MCAO mice were detected. RMST and PIK3R1 were elevated, miR-221-3p was downregulated, and TGF-beta pathway was activated in mice after MCAO. Restored miR-221-3p or depleted RMST improved neurological behavioral functions, relieved pathological injury in brain tissue, and repressed oxidative stress and inflammation in mice after MCAO. Depleted PIK3R1 or restored miR-221-3p offsets the negative effects of overexpressed RMST on mice with MCAO. The present work highlights that RMST augments IS through reducing miR-221-3p-mediated regulation of PIK3R1 and activating TGF-beta pathway.

Automated summary

This study investigated the role of long non-coding RNA RMST in ischemic stroke through the miR-221-3p/PIK3R1/TGF-beta axis in MCAO mice. The results showed that elevated RMST and PIK3R1, downregulated miR-221-3p, and activated TGF-beta pathway were associated with MCAO, and restoring miR-221-3p or depleting RMST improved neurological functions and pathological damage. Additionally, depleting PIK3R1 or restoring miR-221-3p could counteract the negative effects of RMST overexpression in MCAO mice.