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An Interaction Network Driven Approach for Identifying Cervical, Endometrial, Vulvar Carcinomic Biomarkers and Their Multi-targeted Inhibitory Agents from Few Widely Available Medicinal Plants

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Abstract

Differently expressed genes (DEGs) across cervical (CC), endometrial (EC), and vulvar carcinoma (VC) may serve as potential biomarkers for these progressive tumor conditions. In this study, DEGs of cervical (CC), endometrial (EC), and vulvar carcinoma (VC) were identified by microarray analysis. The interaction network between the identified 124 DEGs was constructed and analyzed to identify the hub genes and genes with high stress centrality. DEGs, namely, CDK1 and MMP9, were found to show highest degree and highest stress centrality respectively from the gene interaction network of 124 nodes and 1171 edges. DEG CDK1 is found to be overlapping in both cervical and endometrial carcinomic conditions while DEG MMP9 is found in vulvar carcinomic condition. Further, as it is studied that many phytochemicals play an important role as medicinal drugs, we have identified phytochemicals from few widely available medicinal plants and performed comprehensive computational study to identify a multi-targeted phytochemical against the identified DEGs, which are crucially responsible for the progression of these carcinomic conditions. Virtual screening of the phytochemicals against the target DEG protein structures with PDB IDs 4Y72 and 1GKC resulted in identifying the multi-targeted phytochemical against both the proteins. The molecular docking and dynamics simulation studies reveal that luteolin can act as a multi-targeted agent. Thus, the interactional and structural insights of luteolin toward the DEG proteins signify that it can be further explored as a multi-targeted agent against the cervical, endometrial, and vulvar carcinoma.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements

The research work was carried out in the Laboratory of Chemistry, Department of Applied Sciences, Indian Institute of Information Technology Allahabad, Prayagraj, India. The molecular dynamic simulation results reported in this work were performed on the Central Computing Facility of IIITA, Prayagraj.

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  1. Department of Applied Sciences, Indian Institute of Information Technology Allahabad, Prayagraj, India

    Anamika Mishra, Viswajit Mulpuru & Nidhi Mishra

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  1. Anamika Mishra
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Contributions

A.M. and N.M. conceived the study, A.M. took part in the network analysis and the docking studies, and V.M. took part in the molecular dynamics simulation studies. A.M. and V.M. wrote the main manuscript and prepared the figures. All authors reviewed the manuscript.

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Correspondence to Nidhi Mishra.

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Mishra, A., Mulpuru, V. & Mishra, N. An Interaction Network Driven Approach for Identifying Cervical, Endometrial, Vulvar Carcinomic Biomarkers and Their Multi-targeted Inhibitory Agents from Few Widely Available Medicinal Plants. Appl Biochem Biotechnol 195, 6893–6912 (2023). https://doi.org/10.1007/s12010-023-04441-w

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