CircUBAP2-mediated competing endogenous RNA network modulates tumorigenesis in pancreatic adenocarcinoma

Abstract

We investigated the role of the competing endogenous RNA (ceRNA) network in the development and progression of pancreatic adenocarcinoma (PAAD). We analyzed the expression profiles of PAAD and normal pancreatic tissues from multiple GEO databases and identified 457 differentially expressed circular RNAs (DEcircRNAs), 19 microRNAs (DEmiRNAs) and 1993 mRNAs (DEmRNAs). We constructed a ceRNA network consisting of 4 DEcircRNAs, 3 DEmiRNAs and 149 DEmRNAs that regulates the NF-kappa B, PI3K-Akt, and Wnt signaling pathways. We then identified and validated five hub genes, <i>CXCR4</i>, <i>HIF1A</i>, <i>ZEB1</i>, <i>SDC1</i> and <i>TWIST1</i>, which are overexpressed in PAAD tissues. The expression of <i>CXCR4</i>, <i>HIF1A</i>, <i>ZEB1,</i> and <i>SDC1</i> in PAAD was regulated by <i>circ-UBAP2</i> and <i>hsa-miR-494</i>. The expression of <i>CXCR4</i> and <i>ZEB1</i> correlated with the levels of M2 macrophages, T-regulatory cells (Tregs) and exhausted T cells in the PAAD tissues. The expression of <i>CXCR4</i> and ZEB1 positively correlated with the expression of <i>CTLA-4</i> and <i>PD-1</i>. This suggests that <i>CXCR4</i> and <i>ZEB1</i> proteins inhibit antigen presentation and promote immune escape mechanisms in PAAD cells. In summary, our data suggest that the <i>circUBAP2</i>-mediated ceRNA network modulates PAAD by regulating the infiltration and function of immune cells.