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

Area of Science:

• Oncology
• Pharmacology
• Genomics

Background:

• Liver cancer is a leading cause of cancer-related death globally.
• Late-stage diagnosis significantly worsens liver cancer prognosis.
• Scutellarein (SCU), a natural product, has low toxicity and potential therapeutic applications.

Purpose of the Study:

• To identify pharmacological targets of scutellarein (SCU) in liver cancer.
• To elucidate the biological networks influenced by SCU in liver cancer cells.
• To explore SCU as a potential therapeutic agent for liver cancer.

Main Methods:

• RNA sequencing (RNA-seq) was employed to identify differentially expressed genes in SCU-treated HepG2 cells.
• Gene Ontology (GO) enrichment analysis was performed on differentially expressed genes.
• Protein-protein interaction network analysis was conducted using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING).
• Western blotting was used for validation of identified targets.

Main Results:

• A total of 463 differentially expressed genes were identified: 288 upregulated and 175 downregulated.
• GO analysis indicated involvement in protein heterodimerization activity and nucleosome regulation.
• Histone H1-4 and protein tyrosine phosphatase receptor type C were identified as crucial interacting hub targets.

Conclusions:

• SCU influences key biological processes and targets in liver cancer cells.
• RNA-seq and bioinformatics tools are valuable for identifying novel liver cancer therapeutic targets.
• Histone H1-4 and protein tyrosine phosphatase receptor type C are potential pharmacological targets for SCU in liver cancer treatment.