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

Accumulation of amyloid beta-peptide (A beta) 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 A beta 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 A beta-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 A beta 40, A beta 42, beta-site APP-cleaving enzyme 1 (BACE1), soluble amyloid precursor protein beta (sAPP beta), and membrane-associated APP beta-carboxyl terminal fragment (beta CTF) 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 A beta. Therefore, miR-98-5p may be a novel therapeutic target for AD.