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NQO1 regulates expression and alternative splicing of apoptotic genes associated with Alzheimer's disease in PC-12 cells

ABSTRACT: Quinone oxidoreductase I (NQO1), an important antioxidant enzyme which plays an important role in monitoring cellular redox state, was altered in the brain tissues of Alzheimer’s disease (AD) patients. In addition to its traditional antioxidant effect, NQO1 is also a multifunctional RNA-binding protein (RBP) in post-transcriptional regulation. However, NQO1 in AD pathology by acting as an RBP is not studied. In the present study, the RBP functions of NQO1 in rat PC12 cells, a cell line widely used in neurological disease studies, were investigated using siRNA knock-down (KD) and following whole transcriptome (RNA-seq) analysis. Reduced levels of NQO1 led to a significant increase in cellular apoptosis, compared with control cells. Notably, RNA-seq analysis of the transcriptome of PC12 cells by NQO1-KD revealed that genes in certain apoptosis pathways, were under global transcriptional and alternative splicing regulation. Quantitative RT-PCR confirmed the NQO1-regulated transcription of apoptotic genes Cryab, Lgmn , Ngf, Apoe, Brd7, Stat3, and alternative splicing of Bin1, Picalm, Fyn. These NQO1-regulated genes have been found to be closely related to AD pathogenesis. Our findings suggest that NQO1 acts as an RBP and participates in the pathology of AD by regulating expression and alternative splicing of genes involved in apoptosis. The results of present study extend our understanding of the cellular and molecular mechanisms in AD pathogenesis, which might contribute to the development of novel therapeutic targets.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE185633 | GEO | 2023/10/20

REPOSITORIES: GEO

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