title: Attenuated ability of BACE1 to cleave the amyloid precursor protein via silencing long noncoding RNA BACE1‑AS expression.
abstract: Although large numbers of long noncoding RNAs (lncRNAs) expressed in the mammalian nervous system have been detected, their functions and mechanisms of regulation remain to be fully clarified. It has been reported that the lncRNA antisense transcript for β‑secretase‑1 (BACE1‑AS) is elevated in Alzheimer's disease (AD) and drives the rapid feed‑forward regulation of β‑secretase, suggesting that it is critical in AD development. In the present study, the senile plaque (SP) AD SH‑SY5Y cell model was established using the synthetic amyloid β‑protein (Aβ) 1‑42 in vitro. Using this model, the potential of siRNA‑mediated silencing of lncRNA BACE1‑AS expression to attenuate the ability of β‑secretase‑1 (BACE1) to cleave amyloid precursor protein (APP) and to reduce the production of Aβ1‑42 oligomers was investigated. MTT assays demonstrated that exogenous Aβ1‑42 suppressed SH‑SY5Y cell proliferation and induced APP‑related factor expression and SP formation. Furthermore, quantitative polymerase chain reaction and western blot analysis revealed that the mRNA and protein expression of Aβ1‑42 and Aβ1‑40 was significantly increased in the AD model group, with a marked decrease in Ki‑67 expression at day six. RNase protection assays (RPA) and northern blotting analysis confirmed that exogenous Aβ1‑42 not only promoted the expression of the APP‑cleaving enzyme BACE1, but also induced lncRNA BACE1‑AS expression. Furthermore, lncRNA BACE1‑AS formed RNA duplexes and increased the stability of BACE1 mRNA. Downregulation of lncRNA BACE1‑AS expression in SH‑SY5Y cells by siRNA silencing resulted in the attenuation of the ability of BACE1 to cleave APP and delayed the induction of SP formation in the SP AD SH‑SY5Y cell model.
authors: Central Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors: Te
authors: T
authors: Liu
authors: Central Laboratory, School of Life Science and Technology, Tongji University, Shanghai 200092, P.R. China.
authors: Yongyi
authors: Y
authors: Huang
authors: Central Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors: Jiulin
authors: J
authors: Chen
authors: Central Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors: Huiying
authors: H
authors: Chi
authors: Central Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors: Zhihua
authors: Z
authors: Yu
authors: Central Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors: Jian
authors: J
authors: Wang
authors: Central Laboratory, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors: Chuan
authors: C
authors: Chen
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D020868:Gene Silencing; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019394:Ki-67 Antigen; D010446:Peptide Fragments; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human