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CircRNA-SORE mediates sorafenib resistance inhepatocellular carcinoma by stabilizing YBX1

Signal Transduction and Targeted Therapy 2021年第1期6卷 117-130页

作者： Junjie Xu Lin Ji Yuelong Liang Zhe Wan Wei Zheng Xiaomin Song Kirill Gorshkov Qiming Sun Hui Lin Xueyong Zheng Jiang Chen Ren-an Jin Xiao Liang Xiujun Cai Key Laboratory of Laparoscopic Technology of zhejiang Province Department of General SurgerySir Run-Run Shaw HospitalZhejiang University School of Medicine310016HangzhouChina zhejiang University Cancer center 310016 HangzhouChina zhejiang minimal invasive diagnosis and treantment thechnology research center of severe hepatobiliary disease 310016 HangzhouChina National center for Advancing Translational Sciences National Institutes of Health9800 Medical Center DriveBethesdaMD 20892USA State Key Laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell ScienceInstitute of Biochemistry and Cell BiologyChinese Academy of Sciences200031 ShanghaiChina Department of Biochemistry and Department of Cardiology of the Second Affiliated HospitalZhejiang University School of Medicine310058 HangzhouChina

Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma(HCC).However,sorafenib resistance significantly limits its therapeutic efficacy,and the mechanisms underlying resistance have not been fully *** we report that a circular RNA,circRNA-SORE(a circular RNA upregulated in sorafenib-resistant HCC cells),plays a significant role in sorafenib resistance in *** found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of *** studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm,which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 ***,our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC *** different HCC mouse models,we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib *** study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.

关键词： sorafenib hepatocellular resistance

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