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

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Ischemic stroke (IS) is a major cause of disability, and its underlying mechanisms require further elucidation.
• Long non-coding RNAs (lncRNAs) are emerging as critical regulators in various biological processes, including neurological diseases.

Purpose of the Study:

• To investigate the role of long non-coding RNA rhabdomyosarcoma 2 related transcript (RMST) in ischemic stroke (IS).
• To explore the regulatory axis involving RMST, microRNA-221-3p (miR-221-3p), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and transforming growth factor-β (TGF-β) signaling in IS.

Main Methods:

• Establishment of a middle cerebral artery occlusion (MCAO) mouse model to mimic ischemic stroke.
• Assessment of neurological function, brain tissue pathology, oxidative stress, and inflammation.
• Detection of RMST, miR-221-3p, PIK3R1, and TGF-β pathway-related protein expression in MCAO mouse brains.

Main Results:

• RMST and PIK3R1 expression were upregulated, while miR-221-3p was downregulated in MCAO mice, correlating with activated TGF-β signaling.
• Restoring miR-221-3p or depleting RMST significantly improved neurological function, reduced brain injury, and attenuated oxidative stress and inflammation.
• PIK3R1 depletion or miR-221-3p restoration counteracted the detrimental effects of RMST overexpression in the MCAO model.

Conclusions:

• RMST aggravates ischemic stroke by suppressing miR-221-3p, leading to dysregulation of PIK3R1 and activation of the TGF-β pathway.
• The RMST/miR-221-3p/PIK3R1/TGF-β axis represents a potential therapeutic target for mitigating ischemic stroke progression and damage.