Comprehensive transcriptomic profiling of liver cancer identifies that histone and PTEN are major regulators of SCU‑induced antitumor activity

Oncol Lett. 2024 Jan 11;27(3):94. doi: 10.3892/ol.2024.14227. eCollection 2024 Mar.

Abstract

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.

Keywords: Gene Ontology; HepG2; PTEN; RNA-sequencing; differentially expressed genes; histone; liver cancer.

Grants and funding

This study was supported by the National Research Foundation of Korea funded by the Ministry of Science and ICT (grant nos. 2022R1A6A3A01086899 and RS-2023-0024337661382).