The Journal of Practical Medicine >

2024 , Vol. 40 >Issue 4: 453 - 459

DOI: https://doi.org/10.3969/j.issn.1006-5725.2024.04.003

Feature Reports：Depression

The mechanism of target regulating of miR⁃421 to Menin/Caspase⁃3 pathway for depression

  • Yonghui LIU ,
  • Qingjing TAN ,
  • Qing CHEN ,
  • Liping WEI ,
  • Junwei YANG ,
  • Kan YANG ,
  • Yuguang. GAO
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  • *.Department of Neurology，First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China

Received date: 2023-04-09

  Online published: 2024-03-08

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Abstract

Objective To explore the mechanism of miR-421 affecting the occurrence and development of depression. Methods A depressive rat model was established by single intraperitoneal injection of lipopolysaccharide （LPS）， and depressive behavior was detected by glucose preference test and open-field test. miRNA microarray chips and RT-PCR were used to analyze the expression level of miR-421 in hippocampus of the depressed rats. TargetScan database and mi RDB database were used to predict the target genes of miR-421. Dual luciferase reporter gene assay was used to observe the binding of miR-421 to the target genes. The impact of over-expression and inhibition of miR-421 on target genes was observed， then the influence of over-expression and inhibition of target genes on downstream factors was observed， and the related mechanism of miR-421 on depression was explored. Results miRNA microarray chips and RT-PCR assay showed that miR-421 was highly expressed in the hippocampus of the depressed rats （P < 0.001）， Inhibition of miR-421 expression could significantly restore the body weight and exercise ability of the depressed rats （P < 0.001）. Binding targets of Menin and miR-421 were predicted by TargetScan database， and interaction between Menin and miR-421 was demonstrated by dual-luciferase reporter gene assay. Menin expression was down-regulated while miR-421 was overexpressed （P < 0.001）， whereas it was up-regulated as miR-421 was inhibited （P < 0.001）. qPCR indicated that expressions of Caspase-3 and NF-κB in the hippocampus of the depressed rats was significantly increased （P < 0.001）， and IL-1β expression in the hippocampus was significantly increased （P < 0.01）. When the expression of Menin was inhibited， the expressions of Caspase-3， NF-κB and IL-1β were increased （P < 0.001）， while the expressions of Caspase-3， NF-κB and IL-1β were decreased when Menin was overexpressed （P < 0.001）. Conclusions Inhibition of miR-421 expression can increase Menin expression， decrease Caspase-3 content， and reduce neuroinflammatory response， thereby improving depressive symptoms.

Key words： depression; miR-421; menin; caspase 3; animal experiments; mechanism

Cite this article

Yonghui LIU , Qingjing TAN , Qing CHEN , Liping WEI , Junwei YANG , Kan YANG , Yuguang. GAO . The mechanism of target regulating of miR⁃421 to Menin/Caspase⁃3 pathway for depression[J]. The Journal of Practical Medicine, 2024 , 40(4) : 453 -459 . DOI: 10.3969/j.issn.1006-5725.2024.04.003

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