Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells

Area of Science:

• Oncology
• Epigenetics
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) is a prevalent liver cancer with a poor prognosis.
• Epigenetic alterations are increasingly recognized as critical drivers in HCC development and progression.
• Epigenetic inhibition, particularly targeting bromodomain and extra-terminal (BET) proteins, is a potential therapeutic strategy, though mechanistic insights are needed.

Purpose of the Study:

• To investigate the molecular mechanisms of BET inhibitors in HCC.
• To identify differentially expressed messenger RNAs (DEmRNAs) and long non-coding RNAs (DElncRNAs) in HCC cells treated with BET inhibitors.
• To explore the correlation and functional significance of these shared transcripts for potential therapeutic targets.

Main Methods:

• Utilized the human HCC cell line HepG2.
• Treated cells with three BET inhibitors: JQ1, OTX015, and ABBV-075.
• Analyzed gene expression profiles to identify DEmRNAs and DElncRNAs, followed by correlation analysis and pathway enrichment analysis.

Main Results:

• Identified shared DEmRNAs and DElncRNAs across all three BET inhibitors.
• Observed downregulation of most shared transcripts, including novel ones.
• Functional analysis suggested decreased cell proliferation and adhesion, and increased apoptosis and inflammation.

Conclusions:

• BET proteins significantly regulate genes involved in HCC progression.
• The identified DEmRNAs and DElncRNAs represent potential biomarkers for HCC.
• This study provides a foundation for developing novel therapeutic strategies targeting BET proteins in HCC.