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Effects of miR-150-5p on cerebral infarction rats by regulating the Wnt signaling pathway via p53
1Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, China. sjd7877@163.com.
Objective:
The aim of this study was to screen differentially expressed micro ribonucleic acids (miRNAs) in the plasma of patients with cerebral infarction (CI). In addition, the role of miR-150-5p in the incidence of CI is mainly explored via animal models and molecular biology experiments.
Patients And Methods:
Blood samples were collected from hospitalized patients diagnosed with CI, including 15 CI patients and 15 non-CI patients as negative controls. Differentially expressed miRNAs in the plasma of these subjects were screened by microarray analysis. TargetScan was applied to predict the target genes of miR-150-5p, which were subjected to GO and pathway enrichment analyses using WebGestalt. Sprague-Dawley rats were randomly divided into Sham group (n=20), Control group (n=20), and Experimental group (n=20). CI model in rats was established in the latter two groups. Rats in Experimental group and Control group were intravenously injected with miR-150-5p mimics or miR-negative control (NC), respectively. The expressions of vital genes in the Wnt signaling pathway, including p53, Cyclin D1 (CCND1), c-Myc, β-catenin (CTNNB1) and Survivin were detected by Western blot in rats at 3 d after injection.
Results:
A total of 3,568 differentially expressed miRNAs were detected in the peripheral blood between CI patients and controls, whose 2,100 were upregulated, including miR-150-5p (p<0.05). The target genes of miR-150-5p were involved in molecular pathways, such as the Wnt signaling pathway, carcinogenesis, endocrine regulation, and infection. Compared with rats in Control group, the protein expression of p53 was downregulated (p<0.05), while CCND1, c-Myc, CTNNB1 and Survivin were upregulated (p<0.05) in Experimental group.
Conclusions:
MiR-150-5p regulates the Wnt signaling pathway and participates in cell proliferation and apoptosis by downregulating p53, which may be a potential mechanism of CI induction.
Insights
Micro ribonucleic acid (miRNA) miR-150-5p is upregulated in cerebral infarction (CI) patients and regulates the Wnt signaling pathway. This suggests miR-150-5p may play a role in CI development by affecting cell proliferation and apoptosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Cerebral infarction (CI) is a major cause of disability and mortality worldwide.
- Micro ribonucleic acids (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various diseases, including CI.
Purpose of the Study:
- To identify differentially expressed miRNAs in the plasma of CI patients.
- To investigate the role of miR-150-5p in CI pathogenesis using animal models and molecular biology techniques.
Main Methods:
- Plasma samples from 15 CI patients and 15 controls were analyzed using microarray to screen for differentially expressed miRNAs.
- Target genes of miR-150-5p were predicted and analyzed for pathway enrichment.
- A CI rat model was established, and the effect of miR-150-5p mimics on Wnt signaling pathway gene expression was assessed via Western blot.
Main Results:
- Over 3,500 differentially expressed miRNAs were identified, with 2,100 upregulated, including miR-150-5p.
- miR-150-5p targets were associated with pathways like Wnt signaling, carcinogenesis, and endocrine regulation.
- In the CI rat model, miR-150-5p mimics led to decreased p53 and increased CCND1, c-Myc, CTNNB1, and Survivin protein levels.
Conclusions:
- miR-150-5p is upregulated in CI patients and influences the Wnt signaling pathway.
- Downregulation of p53 and modulation of cell proliferation/apoptosis by miR-150-5p may contribute to CI development.
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