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.

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Background Laparoscopic liver resection has not been widely used because of intraoperative bleeding. This problem should be solved with instruments and techniques that require a short learning curve. Materials and methods The aim of this work was to present the technique used in our center to perform laparoscopic liver resection using the 'curettage and aspiration' technique with laparoscopic Peng's multifunctional operational dissectors and regional occlusion of inflow and outflow. We retrospectively analyzed patients who underwent a laparoscopic liver resection from August 1998 to August 2012, and collected the conversion rate, operating time, blood loss, hospitalization, bile leakage rate, bleeding rate, and other complications on a yearly basis and in total.We used SPSS software to analyze whether there was a significant difference, and summarized the learning curve of laparoscopic liver resection with various procedures. Results We performed 365 cases of laparoscopic liver resection, including left hemihepatectomy, left lateral lobectomy, segmental hepatectomy, non-anatomic liver resection, right hemihepatectomy, and caudate lobectomy. The diseases included liver cancer, hepatolithiasis, liver hemangioma, focal nodular hyperplasia, liver abscess, and metastatic hepatic carcinoma. In total, 63 cases (17.20 %) were converted to open surgery because of severe adhesions, bleeding, or anatomical limitation. Mean blood loss was 370.6 ± 404.0 ml; mean operating time was 150.8 ± 73.0 min; and mean postoperation hospitalization was 9.2 ± 5.3 days. There were four cases (1.32 %) with the complication of bile leakage and two cases of hemorrhage (0.66 %). No intraoperative or postoperative deaths occurred. After finishing 15-30, 43, 35, and 28 cases of laparoscopic left hemihepatectomy, left lateral hepatectomy, non-anatomic liver resection, and segmentectomy, respectively, the average operating time, blood loss, and hospitalization were almost the same as the overall mean results. Conclusion The technique used in our center is a safe, fast, and effective approach to laparoscopic liver resection. Our 14 years of experience demonstrates that this technique can prevent postoperative bleeding and bile leakage. A surgeon can master the skill of laparoscopic left hemihepatectomy, left lateral hepatectomy, non-anatomic liver resection, and segmentectomy after *15-30, 43, 35, and 28 case procedures, respectively.

Dual-specificity phosphatase-1 (DUSP1/MKP1), as a member of the threoninetyrosine dual-specificity phosphatase family, was first found in cultured murine cells. The molecular mechanisms of DUSP1-mediated extracellular signalregulated protein kinases (ERKs) dephosphorylation have been subsequently identified by studies using gene knockout mice and gene silencing technology. As a protein phosphatase, DUSP1 also downregulates p38 MAPKs and JNKs signaling through directly dephosphorylating threonine and tyrosine. It has been detected that DUSP1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. In various human cancers, abnormal expression of DUSP1 was observed which was associated with prognosis of tumor patients. Further studies have revealed its role in tumorigenesis and tumor progression. Besides, DUSP1 has been found to play a role in tumor chemotherapy, immunotherapy, and biotherapy. In this review, we will focus on the function and mechanism of DUSP1 in tumor cells and tumor treatment. Cancer Medicine Open Access 2062