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Updated: Feb 15, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
Targeting BRD4 proteins suppresses the growth of NSCLC through downregulation of eIF4E expression
Zhongyuan Gao1, Ting Yuan2, Xiao Zhou2
1a Department of Pharmacology , Nanjing Medical University , Nanjing , Jiangsu Province , China.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain and extraterminal domain (BET) proteins act as epigenome readers for gene transcriptional regulation. Among BET family members, BRD4 was well studied, but for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E regulates gene translation and has been proved to play an important role in the progression of lung cancer. In this study, we first confirmed that BET inhibitors JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated eIF4E expression. Then we found that knockdown of BRD4 expression using siRNAs inhibited the growth of NSCLCs as well as decreased eIF4E protein levels. Moreover, overexpression of eIF4E partially abrogated the growth inhibitory effect of JQ1, while knockdown of eIF4E enhanced the inhibitory effect of JQ1. Furthermore, JQ1 treatment or knockdown of BRD4 expression decreased eIF4E mRNA levels and inhibited its promoter activity by luciferase reporter assay. JQ1 treatment significantly decreased the binding of eIF4E promoter with BRD4. Finally, JQ1 inhibited the growth of H460 tumors in parallel with downregulated eIF4E mRNA and protein levels in a xenograft mouse model. These findings suggest that inhibition of BET by JQ1, I-BET151, or BRD4 silencing suppresses the growth of non-small cell lung carcinoma through decreasing eIF4E transcription and subsequent mRNA and protein expression. Considering that BET regulates gene transcription epigenetically, our findings not only reveal a new mechanism of BET-regulated eIF4E in lung cancer, but also indicate a novel strategy by co-targeting eIF4E for enhancing BET-targeted cancer therapy.
Insights
Bromodomain and extraterminal domain (BET) inhibitors suppress non-small cell lung cancer growth by downregulating eIF4E transcription. Targeting both BET proteins and eIF4E offers a novel therapeutic strategy for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Lung cancer is a leading cause of cancer death globally.
- Bromodomain and extraterminal domain (BET) proteins regulate gene transcription, but their role in non-small cell lung carcinoma (NSCLC) is unclear.
- eIF4E is crucial for gene translation and lung cancer progression.
Purpose of the Study:
- To investigate the mechanism of BET protein involvement in NSCLC.
- To explore the relationship between BET proteins and eIF4E in NSCLC.
- To evaluate BET inhibitors as a potential therapeutic strategy for NSCLC.
Main Methods:
- Utilized BET inhibitors (JQ1, I-BET151) and BRD4 siRNA in NSCLC cell lines.
- Assessed cell growth, eIF4E expression (mRNA and protein), and promoter activity.
- Performed luciferase reporter assays and xenograft mouse models.
Main Results:
- BET inhibitors and BRD4 knockdown suppressed NSCLC growth and reduced eIF4E levels.
- Overexpression of eIF4E partially reversed JQ1's inhibitory effect, while knockdown enhanced it.
- JQ1 and BRD4 knockdown decreased eIF4E mRNA levels and inhibited its promoter activity, with reduced BRD4 binding.
Conclusions:
- BET inhibition suppresses NSCLC growth by decreasing eIF4E transcription and expression.
- This study reveals a novel mechanism of BET-regulated eIF4E in lung cancer.
- Co-targeting eIF4E presents a promising strategy to enhance BET-targeted cancer therapy.
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