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Published on: July 22, 2016
Lentiviral vector-mediated RBM5 overexpression downregulates EGFR expression in human non-small cell lung cancer
Zhenzhong Su, Jinzhi Yin, Lijing Zhao
1Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, No,218 Ziqiang Street, Nanguan District, Changchun, Jilin 130041, China. kewangm1@hotmail.com.
Background:
RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. Our previous studies suggested that RBM5 expression was negatively correlated with the expression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) tissues. This study was aimed at determining whether RBM5 is able to regulate EGFR expression.
Methods:
Both in vitro and in vivo studies were carried out to determine the effect of RBM5 on the expression of EGFR. Lentiviral vector-mediated RBM5 overexpression was employed in lung adenocarcinoma cell line A549. A549 xenograft mice were treated with recombinant RBM5 plasmid carried by attenuated Salmonella typhi Ty21a. Real-time quantitative polymerase chain reaction and Western blot were carried out to detect RBM5 and EGFR expression.
Results:
Both in vivo and in vitro studies indicated that the expression of EGFR mRNA and protein was decreased significantly in the RBM5 overexpression group compared to control groups as shown by real-time PCR and Western blot analysis. We identified that RBM5 overexpression inhibited EGFR expression both in A549 cells and in A549 xenograft mice model.
Conclusions:
Our study demonstrated that EGFR expression is regulated by RBM5 in lung adenocarcinomas cells either in a direct or indirect way, which might be meaningful with regards to target therapy in lung cancer.
Insights
RNA binding motif 5 (RBM5) suppresses epidermal growth factor receptor (EGFR) expression in lung cancer. Overexpressing RBM5 significantly reduced EGFR levels in cells and mouse models, suggesting a therapeutic target for lung adenocarcinoma.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- RNA binding motif 5 (RBM5) is a tumor suppressor gene.
- RBM5 regulates apoptosis via alternative splicing.
- RBM5 expression inversely correlates with epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate the regulatory role of RBM5 on EGFR expression in lung adenocarcinoma.
Main Methods:
- In vitro and in vivo studies using A549 lung adenocarcinoma cells.
- Lentiviral vector-mediated RBM5 overexpression.
- A549 xenograft mouse model treated with RBM5.
- Real-time quantitative PCR and Western blot analysis.
Main Results:
- RBM5 overexpression significantly decreased EGFR mRNA and protein levels.
- EGFR expression was inhibited by RBM5 in both A549 cells and xenograft mice.
Conclusions:
- EGFR expression is regulated by RBM5 in lung adenocarcinoma.
- This regulation may occur directly or indirectly.
- Findings suggest RBM5's potential as a target for lung cancer therapy.
