TY - JOUR
T1 - Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer
AU - Lyu, Lijuan
AU - Yao, Jia
AU - Wang, Meng
AU - Zheng, Yi
AU - Xu, Peng
AU - Wang, Shuqian
AU - Zhang, Dai
AU - Deng, Yujiao
AU - Wu, Ying
AU - Yang, Si
AU - Lyu, Jun
AU - Guan, Feng
AU - Dai, Zhijun
N1 - Publisher Copyright:
© Copyright © 2020 Lyu, Yao, Wang, Zheng, Xu, Wang, Zhang, Deng, Wu, Yang, Lyu, Guan and Dai.
PY - 2020/8/7
Y1 - 2020/8/7
N2 - 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.
AB - 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.
KW - breast cancer
KW - HLA-DPB1
KW - HLA-DPB2
KW - immune infiltration
KW - prognosis
KW - pseudogene
UR - https://www.scopus.com/pages/publications/85089804778
U2 - 10.3389/fonc.2020.01245
DO - 10.3389/fonc.2020.01245
M3 - 文章
AN - SCOPUS:85089804778
SN - 2234-943X
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1245
ER -
可持续发展目标 3 良好健康与福祉