CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1

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.

Comparison of laparoscopic hepatectomy,percutaneous radiofrequency ablation and open hepatectomy in the treatment of small hepatocellular carcinoma

Objective： Three mainstream techniques-laparoscopic hepatectomy （LH）, percutaneous radiofrequency ablation （pRFA）, and open hepatectomy （OH）--were compared in this study, in terms of their efficacies in the treat- ment of small hepatocellular carcinoma （HCC）. Methods： A comparative study was performed within a total of 94 patients diagnosed with small HCC in our hospital from 2005 to 2010, who underwent LH （28）, RFA （33）, or OH （33）. They had either a single tumor lesion of less than 5 cm or up to three nodules with diameters of less than 3 cm each. Outcomes were carefully evaluated throughout a 3-year follow-up interval and statistically interpreted. Results： The pRFA group had a significantly lower disease-free survival rate compared with the two surgical groups （P=0.001） and significantly shorter overall survival （P=-0.005）, while the LH group and the OH group had no difference in survival results. For patients younger than 60 years old, surgical approaches offered a better long-term overall survival prognosis （P=0.008）. There were no statistically significant differences among the three groups in overall survival for elderly patients （P=0.104）. Conclusions： Among patients with small HCC, LH may provide better curative effects than pRFA without increasing complication rates, pRFA leads to faster recurrence than surgical resections. LH has similar therapeutic effects to OH and causes less trauma. For patients younger than 60 years old, LH may be the best curative treatment. Elderly patients may choose either surgery or pRFA.

CircRNA-SORE mediates sorafenib resistance inhepatocellular carcinoma by stabilizing YBX1

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.