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Multiple system biology approaches reveals the role of the hsa-miR-21 in increasing risk of neurological disorders in patients suffering from hypertension

Journal of Human Hypertension volume 39, pages 432–441 (2025)Cite this article

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Abstract

Hypertension is a prevalent disease that substantially elevates the risk of neurological disorders such as dementia, stroke and Parkinson’s disease. MicroRNAs (miRNAs) play a critical role in the regulation of gene expression related to brain function and disorders. Understanding the involvement of miRNAs in these conditions could provide new insights into potential therapeutic targets. The main objective of this study is to target and investigate microRNAs (miRNAs) associated with neurological disorders in patients suffering from hypertension. The genes involved in hypertension were identified from various databases including GeneCard, MalaCard, DisGeNet, OMIM & GEO2R. The key gene for hypertension was identified using a systems biology approach. Also, potent phytochemical for hypertension was determined by computer-aided drug-designing approach. Functional miRNAs were determined for the key target gene using miRNet analytics platform by hypergeometric tests. Further, the gene-miRNA interaction was determined and enrichment analysis was done. RPS27A was identified as a key target gene for hypertension. Naringenin showed effective molecular interaction with RPS27A with a binding energy score (−6.28). Further, a list of miRNAs which were targeting brain disorders was determined from miRNet. A gene-miRNA network was constructed using the PSRR tool for Parkinson’s Disease, Autism Spectrum Disorder, Acute Cerebral Infarction, ACTH-Secreting Pituitary Adenoma, & Ependymoma. Further, miRNA 21 & miRNA 16 were found to be associated with four of the neurological disorders. The study identifies specific miRNAs that may serve as potential biomarkers for brain disorders in hypertensive patients. Targeting these miRNAs could open new avenues for therapeutic strategies aimed at mitigating neurological damage in this patient population.

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Fig. 1: Major diseases associated with hypertension.
Fig. 2: Schematic workflow of the methodology used to explore the effect of Naringenin on brain miRNAs in hypertension.
Fig. 3: MA plot and Volcano plot of differentially expressed genes (DEGs) identified from GEO2R.
Fig. 4: Identification of the key hub gene RPS27A using Cytohubba analysis.
Fig. 5: Protein modelled structure & validation.
Fig. 6: Predicted molecular interaction between RPS27A and Naringenin.
Fig. 7: Regulatory network of miRNAs targeting the RPS27A gene across various brain disorders.
Fig. 8: Naringenin upregulates brain disorder-linked miRNAs, potentially regulating RPS27A.

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Data availability

The National Center for Biotechnology Information (www.ncbi.nlm.nih.gov) has the data utilized in this investigation.

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Acknowledgements

The benchwork for this investigation was conducted at the Amity Institute of Biotechnology on the campus of Amity University Uttar Pradesh in Lucknow. The authors would like to thank all of the bioinformatics tools and datasets that were used in this study.

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  1. Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, India

    Sanjana Mishra, Prekshi Garg, Mala Trivedi & Prachi Srivastava

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  1. Sanjana Mishra
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Contributions

SM performed data curation, formal analysis, and wrote the original draft. PG contributed to the methodology, interpretation of results, and participated in reviewing and editing the draft. MT reviewed the final version of the manuscript. PS supervised the study and contributed to the review and editing of the final draft. All authors read and approved the final manuscript.

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Correspondence to Mala Trivedi or Prachi Srivastava.

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All methods were performed in accordance with relevant guidelines and regulations. Ethical approval was not required for this study as it involved only computational analyses of publicly available datasets and did not involve human participants or live vertebrates. Therefore, informed consent was not applicable.

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Mishra, S., Garg, P., Trivedi, M. et al. Multiple system biology approaches reveals the role of the hsa-miR-21 in increasing risk of neurological disorders in patients suffering from hypertension. J Hum Hypertens 39, 432–441 (2025). https://doi.org/10.1038/s41371-025-01027-3

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