Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer

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 HLA-DPB2 and its parental gene HLA-DPB1 were overexpressed and correlated with better prognosis in BC. Mechanistically, our results revealed that HLA-DPB2 might serve as an endogenous RNA to increase HLA-DPB1 expression by competitively binding with has-miR-370-3p . Functionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the HLA-DPB2/HLA-DPB1 axis was strongly relevant to immune-related biological functions. Further analysis demonstrated that high expression levels of the HLA-DPB2 and HLA-DPB1 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 HLA-DPB2 can increase the abundance of tumor-infiltrating lymphocytes in the BC microenvironment. Also, the HLA-DPB2 and HLA-DPB1 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 HLA-DPB2 can upregulate HLA-DPB1 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 HLA-DPB2/HLA-DPB1 axis with ICIs may optimize the current immunotherapy for BC.

Construction and analysis of competing endogenous RNA network of MCF‑7 breast cancer cells based on the inhibitory effect of 6‑thioguanine on cell proliferation

“…Hou et al ( 44 ) reported that miR-370-3p expression was increased in cerebral aneurysm tissues compared with normal tissues, and miR-370-3p was involved in the development of cerebral aneurysm by targeting the KDR/AKT signaling pathway. Lyu et al ( 45 ) suggested that miR-370-3p, as a core molecular, played important role in breast cancer. The pseudogene HLA-DPB2 upregulated HLA-DPB1 through sponging miR-370-3p to exert antitumor effect by recruiting tumor-infiltrating immune cells into the breast tumor microenvironment.…”

ncRNAs-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

“…Numerous studies have confirmed that tumor immune cell infiltration could influence the efficacies of chemotherapy, radiotherapy, or immunotherapy and prognosis of cancer patients. [35][36][37] Our work suggested that SEMA3F was significantly positively correlated with various immune cells, including B cell, CD8 + T cell, CD4 + T cell, macrophage, neutrophil, and dendritic cell in HCC. Moreover, SEMA3F was also markedly positively associated with biomarkers of these infiltrated immune cells.…”

Integrated Profiling Identifies CCNA2 as a Potential Biomarker of Immunotherapy in Breast Cancer

“…TILs present pre-existing immunity and are useful markers response to immunotherapy in breast cancer, especially for TNBC. 36 , 37 The subgroups of TILs in the tumor microenvironment mainly include CD4 + cell, CD8 + cell, and regulatory T cell. Our results show that the key module was mostly related to activated and memory CD4 + T cells.…”