LncRNA NEAT1 induces autophagy through epigenetic regulation of autophagy-related gene expression in neuroglial cells.

Endocytosis and autophagy are two important pathways for amyloid-β (Aβ) clearance in neuroglial cells. Our previous study demonstrated that nuclear paraspeckle assembly transcript 1 (NEAT1) long noncoding RNA modulates Aβ clearance mediated by neuroglial cells via the epigenetic regulation of endocytosis-related genes. Herein, we demonstrate that NEAT1 functions as an autophagy inducer by modulating the expression of multiple autophagy-related genes, including autophagy-related 5 (atg5), autophagy-related 3 (atg3), and beclin1. NEAT1 can promote transcription of these genes by altering histone modification near these transcriptional start sites of the genes and thereby influencing the recruitment of signal transducer and activator of transcription 3 to these gene promoters. Our findings demonstrate a new cellular function of NEAT1 in neuroglial cells and suggest a potential therapeutic target for the treatment of autophagy-related diseases.