PMID- 30975733
OWN - NLM
STAT- MEDLINE
DCOM- 20200807
LR  - 20200807
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 6
DP  - 2019 Jun 28
TI  - MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron 
      proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway 
      by LEPR.
LID - BSR20181904 [pii]
LID - 10.1042/BSR20181904 [doi]
AB  - Autism is known as a severe neurobehavioral syndrome, with males affected more 
      often than females. Previous studies have revealed that microRNAs (miRNAs) play a 
      critical role in the search for novel therapeutic strategies for autism. 
      Therefore, we evaluate the ability of miR-153 to influence brain-derived 
      neurotrophic factor (BDNF) of autism as well as proliferation and apoptosis of 
      hippocampal neuron through the janus kinase-signal transducer and activator of 
      transcription (JAK-STAT) signaling pathway by targeting leptin receptor (LEPR). 
      Firstly, the autistic mice models were established and Morris water maze was 
      employed for the analysis of the learning ability and memory of the mice. 
      Besides, in vitro experiments were conducted with the transfection of different 
      mimic, inhibitor, or siRNA into the hippocampal neuron cells, after which the 
      effect of miR-153 on LEPR and the JAK-STAT signaling pathway-related factors was 
      investigated. Next, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide 
      assay and flow cytometry assay were conducted to evaluate cell proliferation, 
      cell cycle, and apoptosis respectively following transfection. The results 
      revealed that there was a significant decrease in learning ability and memory in 
      the autistic mice along with a reduction in the positive expression rate of BDNF 
      and serious inflammatory reaction. LEPR was confirmed as a target gene of miR-153 
      by the dual luciferase reporter gene assay. After transfection of overexpressed 
      miR-153, LEPR and the JAK-STAT signaling pathway were inhibited followed by an 
      increase in BDNF and enhancement of cell proliferation. In conclusion, the high 
      expression of miR-153 can inhibit activation of JAK-STAT signaling pathway by 
      LEPR, thus improving BDNF expression and the proliferative ability of hippocampal 
      neurons.
CI  - (c) 2019 The Author(s).
FAU - You, Yu-Hui
AU  - You YH
AD  - Department of Paediatric Rehabilitation, Affiliated Hospital of Jining Medical 
      University, Jining 272029, P.R. China.
FAU - Qin, Zhi-Qiang
AU  - Qin ZQ
AD  - Department of Paediatric Rehabilitation, Affiliated Hospital of Jining Medical 
      University, Jining 272029, P.R. China.
FAU - Zhang, Huan-Li
AU  - Zhang HL
AD  - Department of Paediatric Rehabilitation, Affiliated Hospital of Jining Medical 
      University, Jining 272029, P.R. China.
FAU - Yuan, Zhao-Hong
AU  - Yuan ZH
AD  - Department of Paediatric Rehabilitation, Affiliated Hospital of Jining Medical 
      University, Jining 272029, P.R. China.
FAU - Yu, Xin
AU  - Yu X
AUID- ORCID: 0000-0002-1972-5576
AD  - Department of Paediatric Rehabilitation, Affiliated Hospital of Jining Medical 
      University, Jining 272029, P.R. China yuxin_jn@163.com.
LA  - eng
PT  - Journal Article
DEP - 20190625
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (MIRN153 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Leptin)
RN  - 0 (STAT Transcription Factors)
RN  - 0 (leptin receptor, mouse)
RN  - EC 2.7.10.2 (Janus Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Autistic Disorder/*genetics/pathology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cell Cycle/genetics
MH  - Cell Proliferation/genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation/genetics
MH  - Hippocampus/metabolism/pathology
MH  - Humans
MH  - Janus Kinases/genetics
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Neurons/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Leptin/*genetics
MH  - STAT Transcription Factors
PMC - PMC6591574
OTO - NOTNLM
OT  - Autism
OT  - Brain-derived neurotrophic factor
OT  - Hippocampal neurons
OT  - JAK-STAT signaling pathway
OT  - Proliferation
OT  - microRNA-153
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/04/13 06:00
MHDA- 2020/08/08 06:00
PMCR- 2019/06/25
CRDT- 2019/04/13 06:00
PHST- 2018/10/19 00:00 [received]
PHST- 2019/02/28 00:00 [revised]
PHST- 2019/04/06 00:00 [accepted]
PHST- 2019/04/13 06:00 [pubmed]
PHST- 2020/08/08 06:00 [medline]
PHST- 2019/04/13 06:00 [entrez]
PHST- 2019/06/25 00:00 [pmc-release]
AID - BSR20181904 [pii]
AID - 10.1042/BSR20181904 [doi]
PST - epublish
SO  - Biosci Rep. 2019 Jun 25;39(6):BSR20181904. doi: 10.1042/BSR20181904. Print 2019 
      Jun 28.