期刊
EXPERIMENTAL AND THERAPEUTIC MEDICINE
卷 14, 期 4, 页码 3688-3698出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2017.4977
关键词
let-7a; beta-amyloid 1-40; Alzheimer's disease; autophagy; phosphoinositide-3-kinase/Akt/mammalian target of rapamycin
Increased deposition of beta-amyloid (A beta) protein is one of the typical characteristics of Alzheimer's disease (AD). Recent evidence has demonstrated that the microRNA let-7 family, which is highly expressed in the central nervous system, participates in the regulation of pathologic processes of AD. In the present study, the effect of let-7a overexpression on A beta 1-40-induced neurotoxicity was evaluated in PC12 and SK-N-SH cells. The results indicated that overexpression of let-7a enhanced the neurotoxicity induced by A beta 1-40 in PC12 and SK-N-SH cells. In addition, the apoptosis induced by A beta 1-40 in PC12 and SK-N-SH cells was increased by let-7a overexpression. Furthermore, A beta 1-40 treatment increased the protein levels of microtubule-associated protein 1A/1B-light chain 3 (LC3) and beclin-1 and increased the LC3 II/I ratio. The mRNA expression levels of beclin-1, autophagy protein 5 (Atg-5) and Atg-7 were also increased by A beta 1-40 treatment in PC12 cells. Let-7a overexpression further upregulated the above autophagy-related markers. Furthermore, the protein level of p62 was increased by A beta 1-40 treatment, and this was further enhanced by let-7a overexpression. Finally, the present results demonstrated that the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in the autophagy regulation by let-7a. In conclusion, the present study demonstrates that the neurotoxicity induced by A beta 1-40 is augmented by let-7a overexpression via regulation of autophagy, and the PI3K/Akt/mTOR signaling pathway also serves a function in this process.
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