PMID- 29217406
OWN - NLM
STAT- MEDLINE
DCOM- 20190321
LR  - 20220330
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 68
DP  - 2018 Sep
TI  - LncRNA SNHG1 promotes alpha-synuclein aggregation and toxicity by targeting 
      miR-15b-5p to activate SIAH1 in human neuroblastoma SH-SY5Y cells.
PG  - 212-221
LID - S0161-813X(17)30235-8 [pii]
LID - 10.1016/j.neuro.2017.12.001 [doi]
AB  - Numerous long non-coding RNAs (lncRNAs) have been identified as aberrantly 
      expressed in Parkinson's disease (PD). However, limited knowledge is available 
      concerning the roles of dysregulated lncRNAs and the underlying molecular 
      regulatory mechanism in the pathological process of PD. In this study, we found 
      that lncRNA small nucleolar RNA host gene 1 (SNHG1) and seven in absentia homolog 
      1 (SIAH1) were upregulated, but microRNA-15b-5p (miR-15b-5p) was downregulated in 
      SH-SY5Y cells pretreated with MPP+, as well as in MPTP-induced mouse model of PD. 
      Overexpression of SIAH1 enhanced cellular toxicity of alpha-synuclein in SH-SY5Y 
      cells, as indicated by the reduction of cell viability and elevation of LDH 
      release. The percentage of alpha-synuclein aggregate-positive cells and the number of 
      alpha-synuclein aggregates per cell were increased in SH-SY5Y cells transfected with 
      pcDNA-SIAH1, while decreased after transfection with short interfering RNA 
      specific for SIAH1 (si-SIAH1). Bioinformatics and luciferase reporter assay 
      revealed that SIAH1 was a direct target of miR-15b-5p. We also found that SNHG1 
      could directly bind to miR-15-5p and repress miR-15-5p expression. Upregulation 
      of miR-15b-5p alleviated alpha-synuclein aggregation and apoptosis by targeting SIAH1 
      in SH-SY5Y cells overexpressing alpha-synuclein. Overexpression of SNHG1 enhanced, 
      whereas SNHG1 knockdown inhibited alpha-synuclein aggregation and alpha-synuclein-induced 
      apoptosis. Moreover, the neuroprotective effect of si-SNHG1 was abrogated by 
      downregulation of miR-15b-5p. In summary, our data suggest that SNHG1, as a 
      pathogenic factor, promotes alpha-synuclein aggregation and toxicity by targeting the 
      miR-15b-5p/SIAH1 axis, contributing to a better understanding of the mechanisms 
      of Lewy body formation and loss of dopaminergic neurons in PD.
CI  - Copyright (c) 2017. Published by Elsevier B.V.
FAU - Chen, Yuan
AU  - Chen Y
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan Province, PR China.
FAU - Lian, Ya-Jun
AU  - Lian YJ
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan Province, PR China. Electronic address: lianyj@yeal.net.
FAU - Ma, Yun-Qing
AU  - Ma YQ
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan Province, PR China.
FAU - Wu, Chuan-Jie
AU  - Wu CJ
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan Province, PR China.
FAU - Zheng, Ya-Ke
AU  - Zheng YK
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan Province, PR China.
FAU - Xie, Nan-Chang
AU  - Xie NC
AD  - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, Henan Province, PR China.
LA  - eng
PT  - Journal Article
DEP - 20171205
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (MIRN15 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (alpha-Synuclein)
RN  - 0 (long non-coding RNA SNHG1, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (seven in absentia proteins)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation
MH  - Male
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Parkinson Disease/*metabolism
MH  - Parkinsonian Disorders/metabolism
MH  - Protein Aggregation, Pathological/metabolism
MH  - RNA, Long Noncoding/*metabolism
MH  - Ubiquitin-Protein Ligases/*metabolism
MH  - alpha-Synuclein/*metabolism/*toxicity
OTO - NOTNLM
OT  - SIAH1
OT  - lncRNA SNHG1
OT  - miR-15b-5p
OT  - alpha-synuclein
EDAT- 2017/12/09 06:00
MHDA- 2019/03/22 06:00
CRDT- 2017/12/09 06:00
PHST- 2017/08/12 00:00 [received]
PHST- 2017/11/23 00:00 [revised]
PHST- 2017/12/03 00:00 [accepted]
PHST- 2017/12/09 06:00 [pubmed]
PHST- 2019/03/22 06:00 [medline]
PHST- 2017/12/09 06:00 [entrez]
AID - S0161-813X(17)30235-8 [pii]
AID - 10.1016/j.neuro.2017.12.001 [doi]
PST - ppublish
SO  - Neurotoxicology. 2018 Sep;68:212-221. doi: 10.1016/j.neuro.2017.12.001. Epub 2017 
      Dec 5.