Circular RNAs (circRNAs) have emerged as important regulators of various cellular processes and have been implicated in cancer. Previously, we reported the discovery of several dysregulated circRNAs including circPABPC1 (polyadenylate-binding protein 1) in human hepatocellular carcinoma (HCC), although their roles in HCC development remained unclear. Here, we show that circPABPC1 is preferentially lost in tumor cells from clinical samples and inhibits both intrahepatic and distant metastases in a mouse xenograft model. This tumor-suppressive function of circPABPC1 can be attributed to its inhibition of cell adhesion and migration through down-regulating a key member of the integrin family, ITGB1 (β1 integrin). Mass spectrometry and biochemical evidence demonstrate that circPABPC1 directly links ITGB1 to the 26S proteasome for degradation in a ubiquitination-independent manner. Our data have revealed an uncanonical route for integrin turnover and a previously unidentified mode of action for circRNAs in HCC that can be harnessed for anticancer treatment.

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BackgroundMinimally invasive pancreatoduodenectomy (MIPD) has been gradually attempted. However, whether MIPD is superior, equal or inferior to its conventional open pancreatoduodenectomy (OPD) is not clear.MethodsStudies published up to May 2017 were searched in PubMed, Embase, Cochrane Library, and Web of Science. Main outcomes were comprehensively reviewed and measured including conversion to open approach, operation time (OP), estimated blood loss (EBL), transfusion, length of hospital stay (LOS), overall complications, postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), post-pancreatectomy hemorrhage (PPH), readmission, reoperation and reasons of preoperative death, number of retrieved lymph nodes (RLN), surgical margins, recurrence, and survival. The software of Review Manage version 5.1 was used for meta-analysis.ResultsOne hundred studies were included for systematic review and 26 out of them (totally 3402 cases, 1064 for MIPD, 2338 for OPD) were included for meta-analysis. In the early years, most articles were case reports or non-control case series studies, while in the last 6 years high-volume and comparative researches were increasing gradually. Systematic review revealed conversion rates of MIPD to OPD ranged from 0% to 40%. The mean or median OP of MIPD ranged from 276 to 657 min. The total POPF rates vary between 3.8% and 50% observed in all systematic reviewed studies. Meta-analysis demonstrated MIPD had longer OP (WMD = 99.4 min; 95%CI: 46.0 ~ 152.8, P < 0.01), lower blood loss (WMD = −0.54 ml; 95% CI, −0.88 ~ −0.20 ml; P < 0.01), lower transfusion rate (RR = 0.73, 95%CI: 0.57 ~ 0.94, P = 0.02), shorter LOS (WMD = −3.49 days; 95%CI: -4.83 ~ −2.15, P < 0.01). There was no significant difference in time to oral intake, postoperative complications, POPF, reoperation, readmission, perioperative mortality and number of retrieved lymph nodes.ConclusionOur study demonstrates MIPD is technically feasible and safety on the basis of historical studies. MIPD is associated with less blood loss, faster postoperative recovery, shorter length of hospitalization and longer operation time. These findings are waiting for being confirmed with robust prospective comparative studies and randomized clinical trials.Electronic supplementary materialThe online version of this article (10.1186/s12876-017-0691-9) contains supplementary material, which is available to authorized users.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with gender-related differences in onset and course. Androgen receptor (AR), a male hormone receptor, is critical in the initiation and progression of HCC. The role of AR in HCC has been mechanistically characterized and anti-AR therapies have been developed, showing limited efficacy. Immunotherapy targeting immune checkpoint proteins may substantially improve the clinical management of HCC. The mechanism by which AR influences HCC immune state remains unclear. In this study, we demonstrated that AR negatively regulated PD-L1, by acting as a transcriptional repressor of PD-L1. Notably, AR over-expression in HCC cells enhanced CD8 + T function in vitro. We then verified the AR/PD-L1 correlation in patients. In animal experiment we found that lower AR expressed tumor achieved better response to PD-L1 inhibitor. Thus, AR suppressed PD-L1 expression, possibly contributing to gender disparity in HCC. Better understanding of the roles of AR during HCC initiation and progression will provide a novel angle to develop potential HCC immunotherapies.