Overexpression of let‑7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy

  • Authors:
    • Huizi Gu
    • Lan Li
    • Chen Cui
    • Zihui Zhao
    • Guijun Song
  • View Affiliations

  • Published online on: August 21, 2017     https://doi.org/10.3892/etm.2017.4977
  • Pages: 3688-3698
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Abstract

Increased deposition of β‑amyloid (Aβ) 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 Aβ1‑40‑induced neurotoxicity was evaluated in PC12 and SK‑N‑SH cells. The results indicated that overexpression of let‑7a enhanced the neurotoxicity induced by Aβ1‑40 in PC12 and SK‑N‑SH cells. In addition, the apoptosis induced by Aβ1‑40 in PC12 and SK‑N‑SH cells was increased by let‑7a overexpression. Furthermore, Aβ1‑40 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 Aβ1‑40 treatment in PC12 cells. Let‑7a overexpression further upregulated the above autophagy‑related markers. Furthermore, the protein level of p62 was increased by Aβ1‑40 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 Aβ1‑40 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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October-2017
Volume 14 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Gu H, Li L, Cui C, Zhao Z and Song G: Overexpression of let‑7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy. Exp Ther Med 14: 3688-3698, 2017.
APA
Gu, H., Li, L., Cui, C., Zhao, Z., & Song, G. (2017). Overexpression of let‑7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy. Experimental and Therapeutic Medicine, 14, 3688-3698. https://doi.org/10.3892/etm.2017.4977
MLA
Gu, H., Li, L., Cui, C., Zhao, Z., Song, G."Overexpression of let‑7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy". Experimental and Therapeutic Medicine 14.4 (2017): 3688-3698.
Chicago
Gu, H., Li, L., Cui, C., Zhao, Z., Song, G."Overexpression of let‑7a increases neurotoxicity in a PC12 cell model of Alzheimer's disease via regulating autophagy". Experimental and Therapeutic Medicine 14, no. 4 (2017): 3688-3698. https://doi.org/10.3892/etm.2017.4977