Worldwide, liver cancer is the most frequent fatal malignancy. Liver cancer prognosis is poor because patients frequently receive advanced‑stage diagnoses. The current study aimed to establish the potential pharmacological targets and the biological networks of scutellarein (SCU) in liver cancer, a natural product known to have low toxicity and side effects. To identify the differentially expressed genes between SCU‑treated and SCU‑untreated HepG2 cells, RNA sequencing (RNA‑seq) was carried out. A total of 463 genes were revealed to have differential expression, of which 288 were upregulated and 175 were downregulated in the group that had received SCU treatment compared with a control group. Gene Ontology (GO) enrichment analysis of associated biological process terms revealed they were mostly involved in the regulation of protein heterodimerization activity and nucleosomes. Interaction of protein‑protein network analysis using Search Tool for the Retrieval of Interacting Genes/Proteins resulted in two crucial interacting hub targets; namely, histone H1‑4 and protein tyrosine phosphatase receptor type C. Additionally, the crucial targets were validated using western blotting. Overall, the present study demonstrated that the use of RNA‑seq data, with bioinformatics tools, can provide a valuable resource to identify the pharmacological targets that could have important biological roles in liver cancer.
