Abstract
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases in the world, which seriously affects AD patients’ life quality. Recently, long non-coding RNAs (lncRNAs) have been reported to play a key role in AD pathogenesis, however, the specific mechanism remains unclear. Herein, we aimed to investigate the role of lncRNA NKILA in AD. The learning and memory performance of rats from streptozotocin (STZ)-treated or other treated groups were tested by Morris water maze test. Relative levels of genes and proteins were measured using RT-qPCR and Western blotting. Mitochondrial membrane potential was tested by JC-1 staining. Levels of ROS, SOD, MDA, GSH-Px, and LDH were measured using corresponding commercial kits. Apoptosis was evaluated by TUNEL staining or Flow cytometry assay. RNA Immunoprecipitation (RIP), RNA pulldown, Chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays were utilized to test the interaction between indicated molecules. STZ treatment caused learning and memory impairment in rats and oxidative stress damage in SH-SY5Y cells. LncRNA NKILA was found to be elevated in the hippocampal tissues of rats and SH-SY5Y cells after STZ exposure. Knockdown of lncRNA NKILA alleviated STZ-induced neuronal damage. Furthermore, lncRNA NKILA could bind to ELAVL1, which regulate the stability of FOXA1 mRNA. Moreover, TNFAIP1 transcription process was controlled by FOXA1, which targeted the promoter of TNFAIP1. In vivo results demonstrated that lncRNA NKILA accelerated STZ-induced neuronal damage and oxidative stress by FOXA1/TNFAIP1 axis. Our findings indicated that knockdown of lncRNA NKILA inhibited the neuronal damage and oxidative stress induced by STZ through the FOXA1/TNFAIP1 axis, thereby alleviating the development of AD, revealing a promising therapeutic axis for AD treatment.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported by National Natural Science Foundation of China (82074380, 82074503), Discipline Innovation Team of Shaanxi University of Chinese Medicine (2019-QN05), Key research and development project of Shaanxi Province (2020SF-336, 2023-YBSF-615), Key scientific research project of Shaanxi Provincial Department of Education (22JS010), Scientific research Project of Traditional Chinese Medicine Administration of Shaanxi Province (SZY-KJCYC-2023-064), Key research and development plan of Xianyang City (L2022ZDYFSF055), School-level Scientific Research Project of Shaanxi University of Chinese medicine (2020GP41, 2021GP01).
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Conception of manuscript: all authors. Manuscript design and writing: YZ, YW, YW. Manuscript reviewing and editing: all authors. All authors read and agreed to the final version of the manuscript.
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Zhou, Y., Wang, Y., Wang, Y. et al. LncRNA NKILA Exacerbates Alzheimer’s Disease Progression by Regulating the FOXA1-Mediated Transcription of TNFAIP1. Neurochem Res 48, 2895–2910 (2023). https://doi.org/10.1007/s11064-023-03944-6
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DOI: https://doi.org/10.1007/s11064-023-03944-6