LncRNA XIST knockdown attenuates Aβ25-35-induced toxicity oxidative stress and apoptosis in primary cultured rat hippocampal neurons by targeting miR-132

摘要

Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder. The abnormal accumulation and deposition of amyloid-beta peptide (Aβ) in senile plaques and cerebral vasculature is widely recognized to be the most likely culprit in the pathogenesis of AD. Long non-coding RNAs (lncRNAs), a kind of evolutionarily conserved non-coding RNAs with over 200 nucleotides in length, have introduced a novel field of biology, and are involved in various human diseases, including neurological diseases. Recently, lncRNA X-inactive specific transcript (XIST) is reported to be upregulated in the rat spinal cord injury (a neurological disease) model and XIST knockdown has a prominent protective effect on the recovery of spinal cord injury. However, little is known about the expression and function of XIST in AD. Here, we showed that Aβ treatment increased XIST expression in hippocampal neurons. XIST knockdown ameliorated toxicity, oxidative stress, and apoptosis induced by Aβ treatment in hippocampal neurons. We further identified and confirmed that miR-132 was the target of XIST, and XIST functioned by targeting miR-132. Collectively, these data show that knockdown of XIST relieves Aβ -induced toxicity, oxidative stress, and apoptosis in primary cultured rat hippocampal neurons by upregulation of miR-132. These findings encourage continued investigation of the potential of manipulating XIST in the treatment of AD.