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Attenuated ability of BACE1 to cleave the amyloid precursor protein via silencing long noncoding RNA BACE1‑AS expression

  • Authors:
    • Te Liu
    • Yongyi Huang
    • Jiulin Chen
    • Huiying Chi
    • Zhihua Yu
    • Jian Wang
    • Chuan Chen

  • View Affiliations

  • Published online on: June 23, 2014     https://doi.org/10.3892/mmr.2014.2351
  • Pages: 1275-1281

  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.
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September-2014
Volume 10 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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  • Impact Factor: 3.4
  • Ranked Medicine Research and Experimental
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  • CiteScore: 6.9
  • CiteScore Rank: Q2: #98/328 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.721
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Spandidos Publications style
Liu T, Huang Y, Chen J, Chi H, Yu Z, Wang J and Chen C: Attenuated ability of BACE1 to cleave the amyloid precursor protein via silencing long noncoding RNA BACE1‑AS expression. Mol Med Rep 10: 1275-1281, 2014
APA
Liu, T., Huang, Y., Chen, J., Chi, H., Yu, Z., Wang, J., & Chen, C. (2014). Attenuated ability of BACE1 to cleave the amyloid precursor protein via silencing long noncoding RNA BACE1‑AS expression. Molecular Medicine Reports, 10, 1275-1281. https://doi.org/10.3892/mmr.2014.2351
MLA
Liu, T., Huang, Y., Chen, J., Chi, H., Yu, Z., Wang, J., Chen, C."Attenuated ability of BACE1 to cleave the amyloid precursor protein via silencing long noncoding RNA BACE1‑AS expression". Molecular Medicine Reports 10.3 (2014): 1275-1281.
Chicago
Liu, T., Huang, Y., Chen, J., Chi, H., Yu, Z., Wang, J., Chen, C."Attenuated ability of BACE1 to cleave the amyloid precursor protein via silencing long noncoding RNA BACE1‑AS expression". Molecular Medicine Reports 10, no. 3 (2014): 1275-1281. https://doi.org/10.3892/mmr.2014.2351