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Research Paper|Volume 11, Issue 19|pp 8484—8501

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

Rongjie Zhao1, Junjie Ni2, Si Lu3, Sujing Jiang4, Liangkun You1, Hao Liu1, Jiawei Shou1, Chongya Zhai1, Wei Zhang1, Shengpeng Shao5, Xinmei Yang6, Hongming Pan1, Weidong Han1
  • 1Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, China
  • 2The First Clinical College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
  • 3The Fourth Clinical College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
  • 4Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
  • 5The Second Clinical College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
  • 6Department of Oncology, The First Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, China
* Equal contribution
Received: July 30, 2019Accepted: September 22, 2019Published: October 4, 2019
https://doi.org/10.18632/aging.102334

Copyright © 2019 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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, 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.