scholarly journals The selective Trk inhibitor AZ623 inhibits brain-derived neurotrophic factor-mediated neuroblastoma cell proliferation and signaling and is synergistic with topotecan

Cancer ◽  
2010 ◽  
Vol 117 (6) ◽  
pp. 1321-1391 ◽  
Author(s):  
Peter E. Zage ◽  
Timothy C. Graham ◽  
Lizhi Zeng ◽  
Wendy Fang ◽  
Christine Pien ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Neurotrophic Factor ◽  
Neuroblastoma Cell ◽  
Brain Derived Neurotrophic Factor

scholarly journals MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Yu-Hui You ◽  
Zhi-Qiang Qin ◽  
Huan-Li Zhang ◽  
Zhao-Hong Yuan ◽  
Xin Yu
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Neurotrophic Factor ◽  
Hippocampal Neuron ◽  
Brain Derived Neurotrophic Factor ◽  
Janus Kinase ◽  
Learning Ability ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Stat Signaling

AbstractAutism 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.

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