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Targeting LINC01607 sensitizes hepatocellular carcinoma to Lenvatinib via suppressing mitophagy

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收录情况： ◇ SCIE

作者：
Zhang Yuxin[1,2,4] * ; Zhang Yujie[3] * ; Tao Haisu[1,2,5] * ; Zhu Jinghan[1,2] * ; Lu Yuanxiang[1,2] ; Cheng Fangling[1,2] ; Xiong Yixiao[1,2] ; Liu Junjie[1,2] ; Cai Guangzhen[1,2] ; Zhang Zhanguo[1,2,*2] ; Liang Huifang[1,2,*2] ; Chen Yifa[1,2,*2] ; Zhang Wanguang[1,2,*1] ;
单位： [1]Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China [3]Department of Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [4]Department of Pediatric Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [5]Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
出处：
DOI： 10.1016/j.canlet.2023.216405
ISSN：

关键词： Hepatocellular carcinoma Lenvatinib resistance LINC01607 P62 Nrf2 Mitophagy

摘要：
Lenvatinib is a standard therapy option for advanced hepatocellular carcinoma (HCC), but resistance limits clinical benefits. In this study, we identified inhibition of ROS levels and reduced redox status in Lenvatinib-resistant HCC. Integrating RNA-seq with unbiased whole-genome CRISPR-Cas9 screen analysis indicated LINC01607 regulated the P62 to enhance drug resistance by affecting mitophagy and antioxidant pathways. Underlying mechanisms were investigated both in vitro and in vivo. We initially confirmed that LINC01607, as a competing endogenous RNA (ceRNA) competing with mirRNA-892b, triggered protective mitophagy by upregulating P62, which reduced ROS levels and promoted drug resistance. Furthermore, LINC01607 was proved to resist oxidative stress by regulating the P62-Nrf2 axis, which transcriptionally regulated the expression of LINC01607 to form a positive feedback loop. Finally, silencing LINC01607 combined with Lenvatinib reversed resistance in animal and patient-derived organoid models. In conclusion, we proposed a novel mechanism of Lenvatinib resistance involving ROS homeostasis. This work contributed to understanding redox homeostasis-related drug resistance and provided new therapeutic targets and strategies for HCC patients.Copyright © 2023. Published by Elsevier B.V.

基金：
National Natural Science Foundation of China grants (82173319 and 82303832).
语种：
外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
最新[2025]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
JCR分区：
出版当年[2021]版：
Q1 ONCOLOGY
最新[2024]版：
Q1 ONCOLOGY

影响因子： 最新[2024版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China [4]Department of Pediatric Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China
共同第一作者：
通讯作者：
通讯机构： [1]Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China [*1]No. 1095 Jiefang Avenue, Wuhan, Hubei province, 430030, China. [*2]Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China.
推荐引用方式(GB/T 7714)：
Zhang Yuxin,Zhang Yujie,Tao Haisu,et al.Targeting LINC01607 sensitizes hepatocellular carcinoma to Lenvatinib via suppressing mitophagy[J].CANCER LETTERS.2023,576:doi:10.1016/j.canlet.2023.216405.
APA：
Zhang Yuxin,Zhang Yujie,Tao Haisu,Zhu Jinghan,Lu Yuanxiang...&Zhang Wanguang.(2023).Targeting LINC01607 sensitizes hepatocellular carcinoma to Lenvatinib via suppressing mitophagy.CANCER LETTERS,576,
MLA：
Zhang Yuxin,et al."Targeting LINC01607 sensitizes hepatocellular carcinoma to Lenvatinib via suppressing mitophagy".CANCER LETTERS 576.(2023)

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