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Overexpressed Pseudogene Promotes Tumor Immune Infiltrates by Regulating and Indicates a Better Prognosis in Breast Cancer

Overview
Journal Front Oncol
Specialty Oncology
Date 2020 Sep 9
PMID 32903535
Citations 38
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Abstract

Immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma and non-small cell lung cancer. However, many patients with breast cancer (BC) show low response to ICIs due to the paucity of infiltrating immune cells. Pseudogenes, as a particular kind of long-chain noncoding RNA, play vital roles in tumorigenesis, but their potential roles in tumor immunology remain unclear. In this study that used data from online databases, the novel pseudogene and its parental gene were overexpressed and correlated with better prognosis in BC. Mechanistically, our results revealed that might serve as an endogenous RNA to increase expression by competitively binding with . Functionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the axis was strongly relevant to immune-related biological functions. Further analysis demonstrated that high expression levels of the and were significantly associated with high immune infiltration abundance of CD8+ T cells, CD4+ T cells, Tfh, Th1, and NK cells and with high expression of majority biomarkers of monocytes, NK cell, T cell, CD8+ T cell, and Th1 in BC and its subtype, indicating that can increase the abundance of tumor-infiltrating lymphocytes in the BC microenvironment. Also, the and expression levels positively correlated with the expression levels of programmed cell death protein 1, programmed cell death ligand 1, and cytotoxic T-lymphocyte-associated antigen-4. Our findings suggest that pseudogene can upregulate through sponging has-miR-370-3p, thus exerting its antitumor effect by recruiting tumor-infiltrating immune cells into the breast tumor microenvironment, and that targeting the axis with ICIs may optimize the current immunotherapy for BC.

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