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• W3117640930 abstract "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 clarified. Here 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 HCC. We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib. Further 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 degradation. Moreover, our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells. Using different HCC mouse models, we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance. Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1." @default.
• W3117640930 created "2021-01-05" @default.
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• W3117640930 date "2020-12-26" @default.
• W3117640930 modified "2023-10-14" @default.
• W3117640930 title "CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1" @default.
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• W3117640930 doi "https://doi.org/10.1038/s41392-020-00375-5" @default.
• W3117640930 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7762756" @default.
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