The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression  

作　　者：Shengnan Ren Ya Zhu Siying Wang Qinqiu Zhang Niu Zhang Xiaoteng Zou Chenchen Wei Zhaoxia Wang 

机构地区：[1]Cancer Medical Center,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China [2]Department of Oncology,Sir Run Run Hospital,Nanjing Medical University,Nanjing 210011,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第1期81-90,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.81672307,82072591,and 81703056);the Key Research and Development Plan(Social Development)of Science and Technology Department of Jiangsu Province(No.BE2019760);the“123”Advantageous Disciplines,Core Technologies and“789”Excellent Talent Training Plan of the Second Affiliated Hospital of Nanjing Medical University(No.789ZYRC202090148).

摘　　要：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.

关 键 词：NSCLC gefitinib resistance DUXAP10 EZH2 OAS2 

分 类 号：R734.2[医药卫生—肿瘤]