PMID- 34650678
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211016
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 13
IP  - 9
DP  - 2021
TI  - LncRNA-MIAT regulates the growth of SHSY5Y cells by regulating the miR-34-5p-SYT1 
      axis and exerts a neuroprotective effect in a mouse model of Parkinson's disease.
PG  - 9993-10013
AB  - To examine the neuroprotective roles of lncRNA-MIAT in Parkinson's disease (PD). 
      RNA sequencing expression profiles were utilized to screen the dysregulated 
      lncRNAs in patients with PD and to explore the underlying molecular mechanisms by 
      which the lncRNAs regulate the pathogenesis of PD. 6-hydroxydopamine-induced 
      SH-SY5Y cell lines and a PD mouse model were used to prove how the overexpressing 
      or knocking-down of MIAT produce a marked effect in both in vitro and in vivo 
      experiments. Subsequently, the subcellular localization of MIAT was detected via 
      RNA fluorescence in situ hybridization (FISH) assays. Quantitative PCR, as well 
      as western blotting, were used to determine the expression levels of the 
      associated genes and proteins. We utilized Cell Counting Kit-8 (CCK8) assays to 
      measure the viability of the cells, and the apoptotic rate was determined using 
      Annexin V-FITC/PI double staining. The expressions of tyrosine hydroxylase (TH) 
      and Parkin were quantified in the substantia nigra using immunohistochemical 
      staining. Also, TUNEL staining was performed to visualize the apoptotic cells in 
      the substantia nigra. Compared with the normal rats, the downregulation of MIAT 
      was observed in the cortex, hippocampus, substantia nigra, and striatum of the PD 
      rats. Overexpression of MIAT exhibited a neuroprotective effect on the SH-SY5Y 
      cells. Through RNA-sequencing of the PD mice treated with an overexpression of 
      MIAT and through a differentially expressed genes analysis, it was hypothesized 
      that MIAT could upregulate the expression of synaptotagmin-1 (SYT1) through 
      sponging of miR-34-5p. Interactions between MIAT, miR-34-5p, and SYT1 were 
      confirmed using RIP and dual-luciferase reporter assays. At the same time, the 
      MIAT overexpression group exhibited elevated Parkin and TH protein levels, 
      increased cell viability but a decreased apoptosis rate of the SH-SY5Y cells in 
      contrast with the negative control (NC) group. In vivo, compared with the NC 
      group, the overexpression of MIAT resulted in an increase in the positive rates 
      of Parkin and TH, and the apoptosis was decreased in the PD mice. The behavioral 
      test results showed that the motor coordination and autonomous activity of the 
      mice were enhanced in the MIAT overexpression group compared with the NC group. 
      LncRNA-MIAT regulates the growth of SHSY5Y cells by sponging miR-34-5p which 
      targets SYT1 and exerts a neuroprotective effect in a mouse model of PD.
CI  - AJTR Copyright (c) 2021.
FAU - Shen, Yue'e
AU  - Shen Y
AD  - Department of Neurology, The First Affiliated Hospital, Harbin Medical University 
      Harbin, Heilongjiang Province, China.
FAU - Cui, Xintao
AU  - Cui X
AD  - Department of Orthopedics, The First Affiliated Hospital, Harbin Medical 
      University Harbin, Heilongjiang Province, China.
FAU - Hu, Yuhang
AU  - Hu Y
AD  - Department of Orthopedics, The First Affiliated Hospital, Harbin Medical 
      University Harbin, Heilongjiang Province, China.
FAU - Zhang, Zhizhuang
AU  - Zhang Z
AD  - Department of Orthopedics, The First Affiliated Hospital, Harbin Medical 
      University Harbin, Heilongjiang Province, China.
FAU - Zhang, Zhenyu
AU  - Zhang Z
AD  - Department of Orthopedics, The First Affiliated Hospital, Harbin Medical 
      University Harbin, Heilongjiang Province, China.
LA  - eng
PT  - Journal Article
DEP - 20210915
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC8507009
OTO - NOTNLM
OT  - Long non-coding RNA-myocardial infarction-associated transcript
OT  - Parkinson's disease
OT  - SHSY5Y cells
OT  - microRNA-34-5p
OT  - synaptotagmin-1
COIS- None.
EDAT- 2021/10/16 06:00
MHDA- 2021/10/16 06:01
PMCR- 2021/09/15
CRDT- 2021/10/15 06:36
PHST- 2020/12/31 00:00 [received]
PHST- 2021/06/22 00:00 [accepted]
PHST- 2021/10/15 06:36 [entrez]
PHST- 2021/10/16 06:00 [pubmed]
PHST- 2021/10/16 06:01 [medline]
PHST- 2021/09/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2021 Sep 15;13(9):9993-10013. eCollection 2021.