PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation

	PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation
	Xu, PF; Jiang, LP; Yang, Y; Wu, MG; Liu, BY; Shi, YL; Shen, QS; Jiang, XL; He, YM; Cheng, DT; Xiong, QX; Yang, ZZ; Duan, LC; Lin, J; Zhao, S; Shi, P; Yang, CP; Chen, YB
	2020
发表期刊	THERANOSTICS
ISSN	1838-7640
卷号	10 期号:8 页码:3767-3778
摘要	Purpose: Lung cancer is the leading cause of cancer related deaths worldwide. We have previously identified many differentially expressed genes (DEGs) from large scale pan-cancer dataset using the Cross-Value Association Analysis (CVAA) method. Here we focus on Progestin and AdipoQ Receptor 4 (PAQR4), a member of the progestin and adipoQ receptor (PAQR) family localized in the Golgi apparatus, to determine their clinical role and mechanism in the development of non-small cell lung cancer (NSCLC). Methods: The protein expression profile of PAQR4 was examined by IHC using tissue microarrays, and the effects of PAQR4 on cell proliferation, colony formation and xenograft tumor formation were tested in NSCLC cells. Real-time RT-PCR, co-immunoprecipitation (co-IP) and GST-pulldown assays were used to explore the mechanism of action of PAQR4. Results: We provided evidence showing that PAQR4 is increased in NSCLC cancer cell lines (A549, H1299, H1650, H1975, H358, GLC-82 and SPC-A1), and identified many mutations in PAQR4 in non-small cell lung cancer (NSCLC) tissues. We demonstrated that PAQR4 high expression correlates with a worse clinical outcome, and that its knockdown suppresses cell proliferation by inducing apoptosis. Importantly, overexpressed PAQR4 physically interacts with Nrf2 in NSCLC cells, blocking the interaction between Nrf2 and Keap1. Conclusion: Our results suggest that PAQR4 depletion enhances the sensitivity of cancerous cell to chemotherapy both in vitro and xenograft tumor formation in vivo, by promoting Nrf2 protein degradation through a Keap1-mediated ubiquitination process.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13285
专题	科研部门_肿瘤信号转导（陈勇彬）
推荐引用方式 GB/T 7714	Xu, PF,Jiang, LP,Yang, Y,et al. PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation[J]. THERANOSTICS,2020,10(8):3767-3778.
APA	Xu, PF.,Jiang, LP.,Yang, Y.,Wu, MG.,Liu, BY.,...&Chen, YB.(2020).PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation.THERANOSTICS,10(8),3767-3778.
MLA	Xu, PF,et al."PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation".THERANOSTICS 10.8(2020):3767-3778.

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