The Pseudogene DUXAP10 Contributes to Gefitinib Resistance in NSCLC by Repressing OAS2 Expression

Overview

Journal Acta Biochim Biophys Sin (Shanghai)

Specialties Biochemistry
Biophysics

Date 2022 Dec 6

PMID 36471952

Authors

Shengnan Ren

Ya Zhu

Siying Wang

Qinqiu Zhang

Niu Zhang

Xiaoteng Zou

Chenchen Wei

Zhaoxia Wang

Affiliations

Soon will be listed here.

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 and . 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.

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