SRY-Box 21 Antisense RNA 1 Knockdown Diminishes Amyloid Beta25-35-Induced Neuronal Damage by miR-132/PI3K/AKT Pathway.

Abstract

Our study aimed to explore the function and mechanism of action of long noncoding RNA (lncRNA) SRY-Box 21 antisense RNA 1 (SOX21-AS1) in amyloid beta25-35 (Aβ25-35)-induced neuronal damage. To induce neuronal damage, neuronal cells and differentiated IMR-32 neuroblastoma cells were challenged by Aβ25-35. SOX21-AS1 and miR-132 quantities were detected by quantitative reverse transcription polymerase chain reaction. Cell damage was evaluated by detecting the changes of cell viability, apoptosis, and oxidative stress. Cell viability was measured using cell counting kit-8. Cell apoptosis was evaluated by flow cytometry and caspase-3 activity. The oxidative stress was analyzed by reactive oxygen species level. The expression of proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was examined by western blot. SOX21-AS1 abundance was up-regulated in Aβ25-35-challenged neuronal cells. Silencing of SOX21-AS1 attenuated Aβ25-35-induced viability reduction and promotion of apoptosis and oxidative stress, suggesting that silencing of SOX21-AS1 repressed Aβ25-35-induced neuronal damage. miR-132 quantity was reduced in Aβ25-35-challenged neuronal cells, and negatively controlled by SOX21-AS1. miR-132 knockdown abolished the effect of SOX21-AS1 silencing on Aβ25-35-induced neuronal damage, indicating that SOX21-AS1 controls Aβ25-35-induced neuronal damage via regulating miR-132. The PI3K/AKT signaling was repressed in Aβ25-35-challenged cells, but this effect was counteracted upon overexpression of miR-132. In conclusion, SOX21-AS1 knockdown mitigated Aβ25-35-dependent neuronal cell damage by promoting miR-132/PI3K/AKT pathway.