Related Experiment Video
Updated: Aug 18, 2025
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression
Shengnan Ren1,2, Ya Zhu1, Siying Wang1
1Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
Abstract:
Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI),is the currently recommended first-line therapy for advanced EGFR-mutant lung cancer, and understanding the mechanism of resistance is the key to formulating therapeutic strategies for EGFR-TKIs. In this study, we evaluate the expression patterns and potential biological functions of the pseudogene DUXAP10 in gefitinib resistance. We find that pseudogene DUXAP10 expression is significantly upregulated in NSCLC gefitinib-resistant cells and tissues. Gain and loss of function assays reveal that knockdown of DUXAP10 by siRNA reverses gefitinib resistance both in vitro and in vivo. Furthermore, DUXAP10 interacts with the histone methyltransferase enhancer of zeste homolog 2 (EZH2) to repress the expression of 2',5'-oligoadenylate synthetase (OAS2). Overall, our study highlights the pivotal role of DUXAP10 in gefitinib resistance, and the DUXAP10/EZH2/OAS2 axis might be a promising therapeutic target to overcome acquired gefitinib resistance in NSCLC.
Insights
The pseudogene DUXAP10 is upregulated in non-small cell lung cancer (NSCLC) resistant to gefitinib. Knocking down DUXAP10 can reverse this resistance, suggesting a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is a first-line therapy for advanced EGFR-mutant lung cancer.
- Understanding resistance mechanisms is crucial for developing effective therapeutic strategies against EGFR-TKIs.
Purpose of the Study:
- To investigate the role of the pseudogene DUXAP10 in gefitinib resistance in non-small cell lung cancer (NSCLC).
- To elucidate the molecular mechanisms underlying DUXAP10-mediated gefitinib resistance.
Main Methods:
- Expression analysis of DUXAP10 in gefitinib-resistant NSCLC cells and tissues.
- In vitro and in vivo gain and loss of function assays using siRNA to knockdown DUXAP10.
- Investigation of the interaction between DUXAP10, enhancer of zeste homolog 2 (EZH2), and 2',5'-oligoadenylate synthetase (OAS2).
Main Results:
- DUXAP10 expression was significantly upregulated in gefitinib-resistant NSCLC cells and tissues.
- Knockdown of DUXAP10 using siRNA reversed gefitinib resistance both in vitro and in vivo.
- DUXAP10 was found to interact with EZH2, repressing OAS2 expression.
Conclusions:
- The pseudogene DUXAP10 plays a critical role in acquired gefitinib resistance in NSCLC.
- The DUXAP10/EZH2/OAS2 signaling axis represents a potential therapeutic target for overcoming gefitinib resistance.
