RETRACTED: Long non-coding RNA GAS5 retards neural functional recovery in cerebral ischemic stroke through modulation of the microRNA-455-5p/PTEN axis

Abstract

Cerebral ischemic stroke (IS) threatens the daily life of individuals, with high mortality. Emerging studies have deciphered the independent roles of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5), microRNA (miR)-455-5p and phosphatase and tensin homolog (PTEN) in IS, but the understanding of their integrated function is in its infancy. Therefore, this study focusing on the GAS5/miR-455-5p/PTEN axis was initiated. Middle cerebral artery occlusion (MCAO) models were established by the suture method. GAS5, miR-455-5p and PTEN expression was detected in rat brain tissues after MCAO. Rats were injected with sh-GAS5 or miR-455-5p agomir before MCAO modeling. A neurobehavioral evaluation was conducted, and oxidative stress injury, apoptosis and mitochondrial function were detected in brain tissues of IS rats. The relationships between GAS5 and miR-455-5p, and between miR-455-5p and PTEN were verified. PC12 cells were transfected with sh-GAS5 or miR-455-5p mimic under oxygen and glucose deprivation/reoxygenation (OGD/R) conditions to evaluate cell viability and apoptosis. GAS5 and PTEN expression levels were elevated and miR-455-5p expression was reduced in brain tissues of MCAO rats and OGD/R-induced PC12 cells. GAS5 downregulation or miR-455-5p upregulation improved neurobehavior, attenuated apoptosis and oxidative injury, and relieved mitochondrial damage in brain tissues of IS rats. Silencing GAS5 or restoring miR-455-5p minimized OGD/R-induced cell damage. MiR-455-5p downregulation antagonized the effects of GAS5 inhibition on IS. This work elucidates that GAS5 downregulation upregulates miR-455-5p to repress PTEN expression, in turn attenuating IS, which may broaden the horizon of IS treatment.