miR-421靶向调控Menin/Caspase-3影响抑郁症的机制

doi:10.3969/j.issn.1006-5725.2024.04.003

Abstract

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

CLC Number:

R749

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.

Figures/Tables 7

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Tab.2

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Fig.3

References 26

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基因	引物序列（5′-3′）
Caspase-3	上游GAGCTTGGAACGCGAAGAAA
	下游GAGTCCATCGACTTGCTTCCA
IL-1β	上游TGGCAACTGTCCCTGAACTC
	下游CCCAAGTCAAGGGCTTGGAA
NF-κB	上游GCTTTGGTGCCAGACTTCCT
	下游TGATGTGTTCGTCCCAGGC
miR-421	上游CGCGTGGCAGTGTCTTAGCT
	下游AGTGCAGGGTCCGAGGTATT
内参	上游AGCCCTCCCTTCTCTCGAAT
	下游CCCCACAACACTGCATTCAC

组别	造模前	造模后
对照组	210.40 ± 6.69	227.21 ± 5.57
模型组	209.83 ± 4.21	196.23 ± 5.69^ΔΔΔ
miR-421过表达组	210.45 ± 4.12	186.07 ± 3.78^***
miR-421抑制组	211.23 ± 5.39	226.87 ± 5.82^***
Menin过表达组	211.14 ± 4.93	226.91 ± 4.89^***
Menin抑制组	209.96 ± 4.62	186.12 ± 4.51^***

组别	糖水消耗体积（mL）	糖水偏好率（%）
对照组	14.31 ± 1.12	80.16 ± 5.32
模型组	6.61 ± 0.79^ΔΔΔ	36.79 ± 3.94^ΔΔΔ
miR-421过表达组	3.01 ± 0.50^***	16.53 ± 0.86^***
miR-421抑制组	12.08 ± 0.75^***	70.66 ± 3.72^***
Menin过表达组	12.24 ± 0.58^***	71.05 ± 3.77^***
Menin抑制组	3.11 ± 0.37^***	16.65 ± 1.08^***

组别	运动总距离（CM）	中央区停留时间（%）	中央区停留时间（%）
对照组	1 354.80 ± 281.56	9.78 ± 2.53	3.93 ± 1.40
模型组	678.93 ± 138.28^ΔΔΔ	3.63 ± 1.25^ΔΔΔ	1.63 ± 0.78^ΔΔΔ
miR-421过表达组	350.42 ± 245.43^**	1.60 ± 0.62^**	0.80 ± 0.24^*
miR-421抑制组	1 364.59 ± 428.18^***	10.19 ± 2.27^***	4.13 ± 1.49^***
Menin过表达组	1 477.53 ± 333.41^***	10.41 ± 2.59^***	4.61 ± 1.25^***
Menin抑制组	357.58 ± 240.46^**	1.72 ± 0.55^**	0.84 ± 0.44^*

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

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