Several epidemiological studies have assessed the associations of interleukin (IL) gene polymorphisms with acute pancreatitis (AP) in different populations. However, the results were inconclusive. Therefore, we performed the present study to comprehensively evaluate the associations of IL gene polymorphisms and susceptibility to AP. Systematic searches of the PubMed, Web of Science, Embase, CNKI, CBMdisc and Google Scholar until February 27, 2013, as well as hand searching of the references of identified articles were performed. Data were extracted using standardized forms and odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. All statistical analyses were performed using Stata 11.0. Ten studies were included in our final combined analysis, covering a total of 1,220 AP cases and 1,351 controls. The results showed evidence for significant association between IL-8 -251 T/A (rs4073) polymorphism and AP risk, suggesting that IL-8 -251 A allele was associated with an increased risk of AP (for A allele vs. T allele: OR = 1.36, 95 % CI 1.05-1.76, p = 0.02; for A/A vs. T/T: OR = 2.28, 95 % CI 1.08-4.81, p = 0.03; for A/A+T/A vs. T/T: OR = 1.40, 95 % CI 1.11-1.77, p = 0.005). However, there were no significant associations between IL-1β (IL-1β +3954 C/T (rs1143634) and IL-1β -511 C/T (rs16944)), IL-6 (IL-6 -174 G/C (rs1800795) and IL-6 -634 C/G (rs1800796)) and IL-10 (IL-10 -1082 A/G (rs1800896), IL-10 -819 C/T (rs1800871) and IL-10 -592 C/A (rs1800872)) gene polymorphisms and AP risk. In summary, the current study suggests that the IL-8 -251 T/A polymorphism is associated with an increased risk of AP. In addition, there were no significant associations between IL-1β, IL-6 and IL-10 gene polymorphisms and AP risk.

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Sorafenib, a multi-tyrosine kinase inhibitor, is a standard treatment for advancedhepatocellular carcinoma (HCC), but the clinical response to sorafenib is seriouslylimited by drug-resistance. Programmed death ligand-1 (PD-L1) is one of the mostimportant inhibitory molecules involved in tumor immune evasion. Recently, it has beenreported that PD-L1 could play crucial roles in drug-resistance of many kinds ofcancers. However, the expression, function and regulation of PD-L1 in sorafenibresistanthepatoma cells remain unclear. In this study, we reported that PD-L1 wasoverexpressed in sorafenib-resistant hepatoma cells and shRNA-mediated PD-L1depletion attenuated drug-resistance and suppressed the migration, invasion, colonyformation and tumorigenesis in sorafenib-resistant hepatoma cells in vitro and in vivo.Mechanistic investigations indicated that loss of microRNA-1 (miR-1), a tumorsuppressivemicroRNA, contributed to the PD-L1 up-regulation in sorafenib-resistanthepatoma cells and PD-L1 was a direct regulatory target of miR-1. Further studyrevealed that an oncogenic transcriptional factor: Nuclear factor E2-related factor 2(NRF-2) was induced in sorafenib-resistant hepatoma cell and inhibited expression ofmiR-1 in vitro. From molecular mechanism insight back to the functional verification,we eventually demonstrated that miR-1 executed its tumor suppressive effects on drugresistanceand other malignant properties in sorafenib-resistant hepatoma cells partiallyby PD-L1 inhibition in vitro and in vivo. In conclusion, our data suggested a NRF-2/miR-1/PD-L1 regulatory axis contributed to development and maintenance of drugCopyright© 2020 Cognizant Communication Corporation4ORM-A-3264 Oncology Research E-pubresistance and other tumorigenic properties in sorafenib-resistant hepatoma cells andprovided a potential therapeutic target for overcoming sorafenib resistance in HCC.

a b s t r a c tAlthough microRNA-1 (miR-1) is a known liver cancer suppressor, the role of miR-1 in apoptosis of hepatoma cells has remained largely unknown. Our study shows that ectopic miR-1 overexpression induced apoptosis of liver hepatocellular carcinoma (HepG2) cells. Apoptosis inhibitor 5 (API-5) was found to be a potential regulator of miR-1 induced apoptosis, using a bioinformatics approach. Furthermore, an inverse relationship between miR-1 and API-5 expression was observed in human liver cancer tissues and adjacent normal liver tissues. Negative regulation of API-5 expression by miR-1 was demonstrated to promote apoptosis of HepG2 cells. Our study provides a novel regulatory mechanism of miR-1 in the apoptosis of hepatoma cells.

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