Journal
AGING-US
Volume 11, Issue 19, Pages 8484-8501Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.102334
Keywords
pancreatic adenocarcinoma; circRNA; ceRNA; immune microenvironment
Categories
Funding
- Zhejiang Natural Sciences Foundation [LQ18H160008, LQ17H160011, LY17H160029]
- Ten Thousand Plan Youth Talent Support Program of Zhejiang Province
- Zhejiang Medical and Health Science and Technology Project [2016KYB290, 2016ZDB007, 2017ZD021]
- Zhejiang Medical Innovative Discipline Construction Project-2016
- Hangzhou Health and Family planning and Science and Technology Project [OO20190347]
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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, CXCR4, HIF1A, ZEB1, SDC1 and TWIST1, which are overexpressed in PAAD tissues. The expression of CXCR4, HIF1A, ZEB1, and SDC1 in PAAD was regulated by circ-UBAP2 and hsa-miR-494. The expression of CXCR4 and ZEB1 correlated with the levels of M2 macrophages, T-regulatory cells (Tregs) and exhausted T cells in the PAAD tissues. The expression of CXCR4 and ZEB1 positively correlated with the expression of CTLA-4 and PD-1. This suggests that CXCR4 and ZEB1 proteins inhibit antigen presentation and promote immune escape mechanisms in PAAD cells. In summary, our data suggest that the circUBAP2-mediated ceRNA network modulates PAAD by regulating the infiltration and function of immune cells.
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