Journal of Immunology Research, 2020, Vol.2020 (2020), p.1-12
2020
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- Autor(en) / Beteiligte
- Titel
- Preferential Expression of B7-H6 in Glioma Stem-Like Cells Enhances Tumor Cell Proliferation via the c-Myc/RNMT Axis
- Ist Teil von
- Journal of Immunology Research, 2020, Vol.2020 (2020), p.1-12
- Ort / Verlag
- Cairo, Egypt: Hindawi Publishing Corporation
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- B7 homologue 6 (B7-H6), a newly identified member of the B7 costimulatory molecule family, is not only a crucial regulator of NK cell-mediated immune responses through binding to NKp30 but also has clinical implications due to its abnormal expression in human cancers. Here, we show that B7-H6 expression is abnormally upregulated in glioma tissue and that B7-H6 is coexpressed with stem cell marker Sox2. Intriguingly, B7-H6 was rarely detected on the surface of glioma cell lines but was abundantly expressed in glioma stem-like cells (GSLCs) that were derived from the glioma cell lines in vitro. Surprisingly, B7-H6 was the only one that was preferentially expressed in the GSLCs among the B7 family members. Functionally, knockdown of B7-H6 in GSLCs by siRNAs led to the inhibition of cell proliferation, with decrease in the expression of the oncogene Myc as well as inactivation of PI3K/Akt and ERK/MAPK signaling pathways. Moreover, we determined that three genes CBL (Casitas B-Lineage Lymphoma Proto-Oncogene), CCNT1 (Cyclin T1), and RNMT (RNA guanine-7 methyltransferase) were coexpressed with B7-H6 and c-myc in glioma tissue samples from the TCGA database and found, however that only RNMT expression was inhibited by the knockdown of B7-H6 expression in the GSLCs, suggesting the involvement of RNMT in the B7-H6/c-myc axis. Extending this to 293T cells, we observed that knocking out of B7-H6 with CRISPR-Cas9 system also suppressed cell proliferation. Thus, our findings suggest B7-H6 as a potential molecule for glioma stem cell targeted immunotherapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2314-8861eISSN: 2314-7156DOI: 10.1155/2020/2328675Titel-ID: cdi_doaj_primary_oai_doaj_org_article_bd021cf9ea404323b0855e52040768f7
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, AKT protein, B7 Antigens - metabolism, Brain cancer, c-Myc protein, Cancer, Carboplatin, Cell Line, Tumor, Cell Proliferation, Cell surface, Chemotherapy, Cloning, CRISPR, Cyclin T1, EDTA, Epidermal growth factor, Gene expression, Gene Expression Regulation, Neoplastic, Genes, Glioma, Glioma - genetics, Glioma - metabolism, Glioma cells, Gliomas, Guanine, HEK293 Cells, Humans, Immune response, Immune response (cell-mediated), Immunology, Immunotherapy, Killer cells, Leukemia, Lymphoma, Lymphomas, MAP kinase, MAP Kinase Signaling System, Methyltransferases - metabolism, Myc protein, Natural killer cells, Neoplastic Stem Cells - metabolism, Proto-Oncogene Proteins c-akt - metabolism, Proto-Oncogene Proteins c-myc - metabolism, Purines, Radiation therapy, Ribonucleic acid, RNA, RNA, Small Interfering, siRNA, SOXB1 Transcription Factors - metabolism, Stem cells, Studies, T cells, Transferases, Tumors