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Pancreatic cancer (PC) is a fatal disease; most patients are asymptomatic before the disease enters the advanced stage, but molecular mechanisms of early PC that can be exploited for diagnosis are not clear. Long noncoding RNAs (lncRNAs) play key roles in the progression of PC. In this study, we found that the expression of the lncRNA EPIC1 (Lnc-EPIC1) is high in PC and closely related to tumor size, TNM staging and lymph node metastasis status. Silencing Lnc-EPIC1 by siRNA targeting could significantly inhibit the cell growth and colony formation ability of PC cells and induced G1/S cell cycle arrest and apoptosis in PC cells. Lnc-EPIC1-specific siRNAs could downregulate the expression of cyclins and CDKs, such as CDC20, CDK4 and Cyclin A1. Knocking out YAP1 with the CRISPR/Cas-9 gene editing method recapitulated the effects of the Lnc-EPIC1-specific siRNAs on cell growth, colony formation ability and apoptosis in PC cells. In addition, the Lnc-EPIC1-specific siRNAs did not further inhibit cell growth or promote apoptosis in YAP1-knockout (YAP1-KO) cells. RNA immunoprecipitation (RIP) results showed that there was a direct interaction between Lnc-EPIC1 and YAP1. An Lnc-EPIC1-overexpressing lentiviral vector promoted the growth of PC cells. The results show that Lnc-EPIC1 interacts with YAP1 to promote the progression of PC. Image 1 • Lnc-EPIC1 and YAP1 is highly expressed in pancreatic cancer. • Lnc-EPIC1 may promote tumor progression by promoting cell growth and reducing apoptosis. • Lnc-EPIC1 regulates PC progression by targeting YAP1, which impacts the downstream molecules CDC20, CDK4 and Cyclin A1. [ABSTRACT FROM AUTHOR]

Abstract Background Caspase 3 is not only involved in apoptosis, but also participates in the nonapoptotic functions. Previously, we found that caspase 3 gene knockout mice displayed decreased number of dendritic cells (DCs). However, whether caspase 3 participate in the function of DCs is unclear. Thus, the present study aims to investigate the role of caspase 3 in the maturation and antitumor function of DCs. Methods Caspase 3 gene was overexpressed in DC2.4 cell line through Lentivirus system. The impact of caspase 3 gene overexpression on the biological behavior of DC2.4 cells was determined by CCK-8, colony formation and apoptosis analysis. The impact of caspase 3 gene overexpression on the antigen uptake, maturation, migration, T cell activation of DC2.4 cells was analyzed with phagocytosis, transwell and mixed lymphocyte reaction assay. Tumor growth and tumor infiltrated T cells were also investigated through tumor bearing model. Results Caspase 3 gene overexpression could slightly increase the apoptosis of DC2.4 cells. Antigen uptake capability and maturation of DC2.4 cells were significantly promoted through caspases 3 gene overexpression. However, CXCR4 expression on DC2.4 cells and migration of DC2.4 cells were not influenced. Caspase 3 gene overexpression also enhanced the T cell activation and cytotoxicity of activated T cells. Finally, overexpression of caspase 3 gene significantly increased the tumor suppression of DC2.4 cells, accompanied by increased infiltration of CD4+ and CD8+ Cells in tumor tissue. Conclusion Caspase 3 gene overexpression could promote maturation and enhance antitumor capability of DC2.4 cells. Highlights • Caspase 3 overexpression only slightly influenced apoptosis of DC2.4 cells. • Antigen uptake, maturation and T cell activation of DC2.4 cells were enhanced. • Finally, antitumor immunity of DC2.4 cells were enhanced. [ABSTRACT FROM AUTHOR]