# Deciphering the role of miRNA-mRNA interactions in cerebral vasospasm post intracranial hemorrhage

**Authors:** Xiang Chu, Xiyan Zhu, Honghao Xu, Wenbing Zhao, Debin Guo, Xing Chen, Jinze Wu, Lei Li, Hao Wang, Jun Fei

PMC · DOI: 10.3389/fmolb.2025.1492729 · Frontiers in Molecular Biosciences · 2025-02-06

## TL;DR

This study identifies key miRNA-mRNA interactions involved in cerebral vasospasm after brain hemorrhage, offering insights into potential treatments.

## Contribution

The study uncovers novel miRNA-mRNA regulatory pairs and their roles in cerebral vasospasm pathogenesis.

## Key findings

- 183 differentially expressed genes and 19 miRNAs were identified in cerebral vasospasm.
- Four miRNAs and two mRNAs were experimentally validated as key regulators in cerebral vasospasm.
- The miRNA-mRNA network highlights potential therapeutic targets for cerebral vasospasm.

## Abstract

Cerebral vasospasm (CVS), a serious complication following subarachnoid hemorrhage, is associated with high rates of mortality and disability. Emerging evidence suggests that abnormal miRNA and mRNA are involved in the development of CVS. This study aims to identify essential miRNA-mRNA regulatory pairs that contribute to CVS pathogenesis. We compared the differences between spasm and non-spasm groups after cerebral hemorrhage, identifying 183 differentially expressed genes (DEGs) and 19 differentially expressed miRNAs (DEMs) related to cerebral vasospasm from the GEO database. Further functional enrichment and KEGG analysis revealed that these DEGs were enriched in several terms and pathways, including the PI3K/AKT/mTOR signaling pathway, oxidative phosphorylation pathway, RNA degradation, and folate biosynthesis signaling pathway. By employing the degree scores method for each gene, we identified the top 10 genes and developed a protein-protein interaction (PPI) network. Additionally, we discovered 19 DEMs associated with CVS and integrated them with mRNA dataset analysis to construct a miRNA-mRNA network, which comprised 8 functionally differentially expressed DEMs and 6 target mRNAs. Experimental validation confirmed the significant regulatory roles of four miRNAs (Let-7a-5p, miR-24-3p, miR-29-3p, and miR-132-3p) and two mRNAs (CDK6 and SLC2A1) in the pathogenesis of CVS. In conclusion, this comprehensive study identifies pivotal miRNAs and their target mRNAs associated with CVS through an integrated bioinformatics analysis of miRNA-mRNA co-expression networks. This approach elucidates the intricate molecular mechanisms underlying CVS and uncovers potential therapeutic targets, thereby providing a valuable foundation for refining and optimizing future treatment strategies.

## Linked entities

- **Genes:** CDK6 (cyclin dependent kinase 6) [NCBI Gene 1021], SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513]
- **Diseases:** subarachnoid hemorrhage (MONDO:0005099)

## Full-text entities

- **Genes:** CDK6 (cyclin dependent kinase 6) [NCBI Gene 1021] {aka MCPH12, PLSTIRE}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, MIR1323 (microRNA 1323) [NCBI Gene 100302255] {aka MIRN1323, hsa-mir-1323, mir-1323}
- **Diseases:** cerebral hemorrhage (MESH:D002543), CVS (MESH:D020301), subarachnoid hemorrhage (MESH:D013345), intracranial hemorrhage (MESH:D020300), spasm (MESH:D013035)
- **Chemicals:** folate (MESH:D005492)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11840915/full.md

## References

68 references — full list in the complete paper: https://tomesphere.com/paper/PMC11840915/full.md

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Source: https://tomesphere.com/paper/PMC11840915