Integrative systems biology and transcriptomic database analysis (GEPIA2 and TNMplot) uncover HRAS-driven anticancer mechanisms of anthraquinones in liver cancer.

Authors

Rajani Benchikeri, Charushila V Balikai, Sachin Gudasi, Rohini Kavalapure, Pooja Kagawad, Pothuraju Naresh, Shriram D Ranade

Published in

Naunyn-Schmiedeberg's archives of pharmacology. Jul 22, 2026. Epub Jul 22, 2026.

Abstract

Liver cancer, primarily hepatocellular carcinoma (HCC), remains a major contributor to global cancer mortality, underscoring the need for effective targeted therapies. This study employed an integrative systems biology and transcriptomic approach to investigate the anticancer potential of anthraquinones targeting HRAS in liver cancer. Putative targets of anthraquinones were predicted using Digep-Pred, while liver cancer-associated genes were retrieved from GeneCards, yielding 215 overlapping targets. Protein-protein interaction (PPI) network analysis identified key hub genes, including AKT1, TP53, and HRAS. Gene Ontology and KEGG pathway enrichment analyses revealed significant involvement of PI3K-Akt, MAPK, and Ras signaling pathways, highlighting their roles in tumor progression and therapeutic modulation. Network pharmacology further established HRAS as a central regulatory node. Pan-cancer transcriptomic profiling using GEPIA2 and TNMplot demonstrated significant overexpression and dysregulation of HRAS across multiple cancers, including liver cancer, with strong associations to tumor progression and prognosis. Genomic analysis via cBioPortal revealed mutation hotspots and copy-number-dependent expression patterns influencing HRAS activity. Molecular docking studies indicated that anthraquinones, particularly citreorosein, exhibited strong binding affinity (- 7.431) toward the HRAS active site through key interactions with SER17, LYS16, GLY13, THR35, and GLU31, outperforming standard drugs such as sorafenib. Molecular dynamics simulations confirmed the stability of the HRAS-citreorosein complex, with low RMSD values indicating minimal conformational deviation and stable binding. Dynamic cross-correlation analysis revealed coordinated residue motions and balanced correlated anticorrelated dynamics, supporting structural integrity. Collectively, these findings highlight HRAS as a promising therapeutic target and anthraquinones as potential candidates for liver cancer treatment.

PMID:
42484860
Bibliographic data and abstract were imported from PubMed on 22 Jul 2026.

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