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Updated: Sep 25, 2025
Author Spotlight: Cost-Effective Transcriptomic Drug Screening - Unlocking New Targets
Published on: February 23, 2024
Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells
Mina Baek1,2, Jin Choul Chai3, Hae In Choi4
1Department of Molecular and Life Science, Hanyang University, Ansan, Republic of Korea.
Abstract:
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poor prognosis. Emerging evidence suggests that epigenetic alterations play a crucial role in HCC, suggesting epigenetic inhibition as a promising therapeutic approach. Indeed, the bromodomain and extra-terminal (BET) inhibitors inhibit the proliferation and invasion of various cancers but still lack a strong mechanistic rationale. Here, we identified the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in human HCC cell line HepG2 treated with the BET inhibitors, JQ1, OTX015, or ABBV-075. We analyzed the correlation between DEmRNAs and DElncRNAs in common for the three inhibitors based on their expression profiles and performed functional annotation pathway enrichment analysis. Most of these shared DEmRNAs and DElncRNAs, including some novel transcripts, were downregulated, indicating decreased proliferation/adhesion and increased apoptosis/inflammation. Our study suggests that BET proteins play a crucial role in regulating cancer progression-related genes and provide a valuable resource for novel putative biomarkers and therapeutic targets in HCC.
Insights
Bromodomain and extra-terminal (BET) inhibitors show promise for treating hepatocellular carcinoma (HCC). This study identifies key gene expression changes, revealing potential new therapeutic targets and biomarkers for liver cancer.
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.
