首页|RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells

RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells

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Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)positively affect the initial control of non-small cell lung cancer(NSCLC).Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment.However,the mechanisms that control the resistance of EGFR-TKIs remain largely unknown.RNA structures have widespread and cru-cial functions in many biological regulations;however,the functions of RNA structures in regulat-ing cancer drug resistance remain unclear.Here,the psoralen analysis of RNA interactions and structures(PARIS)method is used to establish the higher-order RNA structure maps of EGFR-TKIs-resistant and-sensitive cells of NSCLC.Our results show that RNA structural regions are enriched in untranslated regions(UTRs)and correlate with translation efficiency(TE).Moreover,yrdC N6-threonylcarbamoyltransferase domain containing(YRDC)promotes resistance to EGFR-TKIs.RNA structure formation in YRDC 3'UTR suppresses embryonic lethal abnormal vision-like 1(ELAVL1)binding,leading to EGFR-TKI sensitivity by impairing YRDC translation.A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide(ASO)to perturb the interaction between RNA and protein.Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by control-ling YRDC mRNA translation in an ELAVL1-dependent manner.

RNA structureEGFR-TKI resistanceNon-small cell lung cancerYRDCELAVL1

Boyang Shi、Ke An、Yueqin Wang、Yuhan Fei、Caixia Guo、Qiangfeng Cliff Zhang、Yun-Gui Yang、Xin Tian、Quancheng Kan

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Department of Pharmacy,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China

Henan Key Laboratory of Precision Clinical Pharmacy,Zhengzhou University,Zhengzhou 450052,China

Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China

MOE Key Laboratory of Bioinformatics,Center for Synthetic and Systems Biology,Beijing Advanced Innovation Center for Structural Biology,Tsinghua-Peking Joint Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing 100084,China

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Province and Ministry Coconstruction Major Program of Medical Science and Technique Foundation of Henan Province,ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaSpecial Fund for Young and Middle School Leaders of Henan Health Commission,China

SBGJ2020010073187080932121001HNSWJW-2020017

2023

10.1016/j.gpb.2022.10.006

基因组蛋白质组与生物信息学报(英文版)
中国科学院北京基因组研究所

基因组蛋白质组与生物信息学报(英文版)

CSTPCDCSCD
影响因子：0.495
ISSN：1672-0229
年,卷(期)：2023.21(4)
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