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miR-98-5p Acts as a Target for Alzheimer’s Disease by Regulating Aβ Production Through Modulating SNX6 Expression

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Abstract

Accumulation of amyloid β-peptide (Aβ) in the brain of Alzheimer disease (AD) patients is believed to be the main pathological feature of the disease. Meanwhile, miR-98-5p dysregulation was found in AD. However, whether miR-98-5p is involved in the accumulation of Aβ in AD, the underlying molecule mechanism remains unclear. In the present study, we confirmed that miR-98-5p negatively regulated sorting nexin 6 (SNX6) expression by targeting the 3′-UTR of SNX6 mRNA. Downregulation of miR-98-5p alleviated Aβ-induced viability inhibition and decreased apoptosis in SK-N-SH and SH-SY5Y cells by upregulating SNX6 expression. Furthermore, downregulation of miR-98-5p decreased SNX6-dependent levels of Aβ40, Aβ42, β-site APP-cleaving enzyme 1 (BACE1), soluble amyloid precursor protein β (sAPPβ), and membrane-associated APP β-carboxyl terminal fragment (βCTF) in SK-N-SH and HEK293 cells. Our findings demonstrate that miR-98-5p modulates SNX6 expression and thus plays a critical role in accumulation of Aβ. Therefore, miR-98-5p may be a novel therapeutic target for AD.

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Acknowledgments

This study was supported by grants from the Natural Science Foundation of Science and Technology Department of Liaoning Province (no. 2013022042).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People’s Republic of China

    Qiushi Li, Xidong Li & Yanhui Zhang

  2. Department of Neurology, Shenyang General Hospital of PLA, Shenyang, Liaoning, 110084, People’s Republic of China

    Li Wang

  3. Department of Anesthesiology, The First Affiliated Hospital of Jinzhou Medical University, 5-2 People Street, Jinzhou, Liaoning, 121000, People’s Republic of China

    Long Chen

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  1. Qiushi Li
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  2. Xidong Li
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  3. Li Wang
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  4. Yanhui Zhang
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Correspondence to Long Chen.

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Li, Q., Li, X., Wang, L. et al. miR-98-5p Acts as a Target for Alzheimer’s Disease by Regulating Aβ Production Through Modulating SNX6 Expression. J Mol Neurosci 60, 413–420 (2016). https://doi.org/10.1007/s12031-016-0815-7

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  • DOI: https://doi.org/10.1007/s12031-016-0815-7

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