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  • Title: Long Non-Coding RNA BACE1-AS Modulates Isoflurane-Induced Neurotoxicity to Alzheimer's Disease Through Sponging miR-214-3p.
    Author: He W, Chi S, Jin X, Lu J, Zheng W, Yan J, Zhang D.
    Journal: Neurochem Res; 2020 Oct; 45(10):2324-2335. PubMed ID: 32681443.
    Abstract:
    Isoflurane, an anesthetic, can aggravate the progression of Alzheimer's disease (AD). Long non-coding RNA β-secretase 1 (BACE1)-antisense transcript (BACE1-AS) and miR-214-3p are related to AD progression. Nevertheless, it is unclear whether BACE1-AS is involved in the development of isoflurane-mediated AD via miR-214-3p. Amyloid beta peptide (Aβ) was employed to construct the AD cell model. The expression of BACE1-AS and miR-214-3p in the plasma of AD patients and SK-N-SH and SK-N-AS cells treated with Aβ and isoflurane was assessed through quantitative reverse transcription polymerase chain reaction (qRT-PCR). The proliferation and apoptosis of Aβ-treated SK-N-SH and SK-N-AS cells were determined via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) or flow cytometry assays, respectively. Protein levels of B cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), CyclinD1, microtubule-associated protein A1/1B-light chain3 (LC3 I/LC3 II), p62 and Beclin1 were detected via western blot analysis. The relationship between BACE1-AS and miR-214-3p was verified by dual-luciferase reporter assay. We found that BACE1-AS was upregulated and miR-214-3p was downregulated in the plasma of AD patients and SK-N-SH and SK-N-AS cells treated with Aβ and isoflurane. Both BACE1-AS depletion and miR-214-3p augmentation restored the suppression of proliferation and the facilitation of apoptosis and autophagy of Aβ-treated SK-N-SH and SK-N-AS cells induced by isoflurane. Importantly, BACE1-AS acted as a sponge for miR-214-3p. Additionally, miR-214-3p silencing reversed the influence of BACE1-AS knockdown on isoflurane-mediated proliferation, apoptosis and autophagy in Aβ-induced SK-N-SH and SK-N-AS cells. In conclusion, BACE1-AS aggravated isoflurane-induced neurotoxicity to AD via sponging miR-214-3p.
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