title: miR-98-5p Acts as a Target for Alzheimer's Disease by Regulating Aβ Production Through Modulating SNX6 Expression.
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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People's Republic of China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People's Republic of China.
authors.forename: Xidong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Shenyang General Hospital of PLA, Shenyang, Liaoning, 110084, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People's Republic of China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Jinzhou Medical University, 5-2 People Street, Jinzhou, Liaoning, 121000, People's Republic of China. dragonchenjz@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; C431150:SNX6 protein, human; D058305:Sorting Nexins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Alzheimer’s disease; SNX6; miR-98-5p; β-Amyloid