The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression
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 ev...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-11-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022176 |
| _version_ | 1797635856997023744 |
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| author | Ren Shengnan Zhu Ya Wang Siying Zhang Qinqiu Zhang Niu Zou Xiaoteng Wei Chenchen Wang Zhaoxia |
| author_facet | Ren Shengnan Zhu Ya Wang Siying Zhang Qinqiu Zhang Niu Zou Xiaoteng Wei Chenchen Wang Zhaoxia |
| author_sort | Ren Shengnan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:26:14Z |
| format | Article |
| id | doaj.art-f6c06c0f986f47ca9e7a0ae4c089a7e5 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:26:14Z |
| publishDate | 2022-11-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-f6c06c0f986f47ca9e7a0ae4c089a7e52023-11-06T08:59:52ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-11-0155819010.3724/abbs.202217620d259ccThe pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expressionRen Shengnan0Zhu Ya1Wang Siying2Zhang Qinqiu3Zhang Niu4Zou Xiaoteng5Wei Chenchen6Wang Zhaoxia7["Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China","Department of Oncology, Sir Run Run Hospital, Nanjing Medical University, Nanjing 210011, China"]["Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"]["Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"]["Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"]["Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"]["Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"]["Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"]["Cancer Medical Center, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"]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. https://www.sciengine.com/doi/10.3724/abbs.2022176NSCLCgefitinib resistanceDUXAP10EZH2OAS2 |
| spellingShingle | Ren Shengnan Zhu Ya Wang Siying Zhang Qinqiu Zhang Niu Zou Xiaoteng Wei Chenchen Wang Zhaoxia The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression Acta Biochimica et Biophysica Sinica NSCLC gefitinib resistance DUXAP10 EZH2 OAS2 |
| title | The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression |
| title_full | The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression |
| title_fullStr | The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression |
| title_full_unstemmed | The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression |
| title_short | The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression |
| title_sort | pseudogene duxap10 contributes to gefitinib resistance in nsclc by repressing oas2 expression |
| topic | NSCLC gefitinib resistance DUXAP10 EZH2 OAS2 |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022176 |
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