Research Paper Volume 11, Issue 16 pp 6422—6439
A disparate role of RP11-424C20.2/UHRF1 axis through control of tumor immune escape in liver hepatocellular carcinoma and thymoma
- 1 The Key Laboratory of Endemic and Ethnic Diseases, Guizhou Medical University, Ministry of Education, Guiyang 550004, China
- 2 The Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang 550004, China
- 3 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China
- 4 Department of Urology, Guizhou Province People’s Hospital, Guiyang 550002, China
Received: July 13, 2019 Accepted: August 9, 2019 Published: August 23, 2019
https://doi.org/10.18632/aging.102197How to Cite
Copyright © 2019 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The immune system is critical in modulating cancer progression. Pseudogenes are a special type of long non-coding RNAs that regulate different tumorigenic processes. However, the potential roles of pseudogenes in tumor-immune interaction remain largely unclear. Here, we reported that pseudogene RP11-424C20.2 and its parental gene UHRF1 were frequently up-regulated and positively correlated in liver hepatocellular carcinoma (LIHC) and thymoma (THYM), but associated with distinct clinical outcomes. We further found that RP11-424C20.2 may act as a competing endogenous RNA (ceRNA) to increase UHRF1 expression through sponging miR-378a-3p. Functional enrichment analysis showed a strong association of UHRF1 with immune-related biological processes. We also observed that UHRF1 expression significantly correlated with immune infiltration, and different types of tumor-infiltrating immune cells displayed different impacts on clinical outcomes. Furthermore, UHRF1 expression in LIHC and THYM showed an opposite correlation with biomarkers from monocyte, dendritic cell, Th1 and T cell exhaustion. Mechanism investigations revealed that RP11-424C20.2/UHRF1 axis regulated immune escape of LIHC and THYM at least partly through IFN-γ-mediated CLTA-4 and PD-L1 pathway. These findings demonstrate a disparate role of RP11-424C20.2/UHRF1 axis in LIHC and THYM via regulating immune infiltrates, and also indicate a therapeutic value for UHRF1 inhibitors in combination with anti-PD-L1/CLTA-4 blockade.
Abbreviations
ACC: adrenocortical carcinoma; ceRNA: competing endogenous RNA; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; LIHC: hepatocellular carcinoma; LUAD: Lung adenocarcinoma; MESO: mesothelioma; PRAD: prostate adenocarcinoma; SARC: sarcoma; SKCM: skin cutaneous melanoma; TCGA: The Cancer Genome Atlas; THYM: thymoma.