PMID- 29042965
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 14
IP  - 4
DP  - 2017 Oct
TI  - Overexpression of let-7a increases neurotoxicity in a PC12 cell model of 
      Alzheimer's disease via regulating autophagy.
PG  - 3688-3698
LID - 10.3892/etm.2017.4977 [doi]
AB  - Increased deposition of beta-amyloid (Abeta) 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 Abeta1-40-induced 
      neurotoxicity was evaluated in PC12 and SK-N-SH cells. The results indicated that 
      overexpression of let-7a enhanced the neurotoxicity induced by Abeta1-40 in PC12 and 
      SK-N-SH cells. In addition, the apoptosis induced by Abeta1-40 in PC12 and SK-N-SH 
      cells was increased by let-7a overexpression. Furthermore, Abeta1-40 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 Abeta1-40 
      treatment in PC12 cells. Let-7a overexpression further upregulated the above 
      autophagy-related markers. Furthermore, the protein level of p62 was increased by 
      Abeta1-40 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 Abeta1-40 is augmented by let-7a overexpression 
      via regulation of autophagy, and the PI3K/Akt/mTOR signaling pathway also serves 
      a function in this process.
FAU - Gu, Huizi
AU  - Gu H
AD  - First Department of Neurology, The Second Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning 116023, P.R. China.
FAU - Li, Lan
AU  - Li L
AD  - First Department of Neurology, The Second Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning 116023, P.R. China.
FAU - Cui, Chen
AU  - Cui C
AD  - First Department of Neurology, The Second Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning 116023, P.R. China.
FAU - Zhao, Zihui
AU  - Zhao Z
AD  - First Department of Neurology, The Second Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning 116023, P.R. China.
FAU - Song, Guijun
AU  - Song G
AD  - First Department of Neurology, The Second Affiliated Hospital of Dalian Medical 
      University, Dalian, Liaoning 116023, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170821
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC5639351
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - autophagy
OT  - let-7a
OT  - phosphoinositide-3-kinase/Akt/mammalian target of rapamycin
OT  - beta-amyloid 1-40
EDAT- 2017/10/19 06:00
MHDA- 2017/10/19 06:01
PMCR- 2017/08/21
CRDT- 2017/10/19 06:00
PHST- 2016/10/19 00:00 [received]
PHST- 2017/06/16 00:00 [accepted]
PHST- 2017/10/19 06:00 [entrez]
PHST- 2017/10/19 06:00 [pubmed]
PHST- 2017/10/19 06:01 [medline]
PHST- 2017/08/21 00:00 [pmc-release]
AID - ETM-0-0-4977 [pii]
AID - 10.3892/etm.2017.4977 [doi]
PST - ppublish
SO  - Exp Ther Med. 2017 Oct;14(4):3688-3698. doi: 10.3892/etm.2017.4977. Epub 2017 Aug 
      21.