The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma
Glioma is a malignant tumor with a high fatality rate, originating in the central nervous system. Even after standard treatment, the prognosis remains unsatisfactory, probably due to the lack of effective therapeutic targets. The family of transmembrane proteins (TMEM) is a large family of genes tha...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1029270/full |
| _version_ | 1797946984298971136 |
|---|---|
| author | Fengdong Yang Xuezhi Zhang Xinzhuang Wang Yake Xue Xianzhi Liu |
| author_facet | Fengdong Yang Xuezhi Zhang Xinzhuang Wang Yake Xue Xianzhi Liu |
| author_sort | Fengdong Yang |
| collection | DOAJ |
| description | Glioma is a malignant tumor with a high fatality rate, originating in the central nervous system. Even after standard treatment, the prognosis remains unsatisfactory, probably due to the lack of effective therapeutic targets. The family of transmembrane proteins (TMEM) is a large family of genes that encode proteins closely related to the malicious behavior of tumors. Thus, it is necessary to explore the molecular and clinical characteristics of newly identified oncogenes, such as transmembrane protein 60 (TMEM60), to develop effective treating options for glioma. We used bioinformatic methods and basic experiments to verify the expression of transmembrane protein 60 in gliomas and its relationship with 1p and 19q (1p19q) status, isocitrate dehydrogenase (IDH) status, patient prognosis, and immune cell infiltration using public databases and clinical samples. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to detect co-expressed genes. Thus, we inhibited the expression of transmembrane protein 60 to observe the proliferation and activity of glioma LN229 cells. We found transmembrane protein 60 was significantly upregulated in glioma compared with that in normal brain tissue at the mRNA. In the subgroups of World Health Organization high grade, isocitrate dehydrogenase wildtype, 1p and 19q non-codeletion, or isocitrate dehydrogenase wild combined with 1p and 19q non-codeletion, the expression of transmembrane protein 60 increased, and the prognosis of glioma patients worsened. In the transmembrane protein 60 high expression group, infiltration of immune cells and stromal cells in the tumor microenvironment increased, tumor purity decreased, and immune cells and pathways were activated. The immune cells mainly included regulatory T-cell, gamma delta T-cell, macrophages M0, neutrophils, and CD8+ T-cells. Overexpression of co-inhibitory receptors (CTLA4, PDL1 and CD96) may promote the increase of depletion of T-cell, thus losing the anti-tumor function in the transmembrane protein 60 high expression group. Finally, we found that transmembrane protein 60 silencing weakened the viability, proliferation, and colony formation of glioma LN229 cells. This is the 0 report on the abnormally high expression of transmembrane protein 60 in glioma and its related clinical features, such as tumor microenvironment, immune response, tumor heterogeneity, and patient prognosis. We also found that transmembrane protein 60 silencing weakened the proliferation and colony formation of glioma LN229 cells. Thus, the new oncogene transmembrane protein 60 might be an effective therapeutic target for the clinical treatment of glioma. |
| first_indexed | 2024-04-10T21:19:38Z |
| format | Article |
| id | doaj.art-6aadc3b418324d678531c45808f523e4 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T21:19:38Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-6aadc3b418324d678531c45808f523e42023-01-20T07:11:29ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011310.3389/fgene.2022.10292701029270The new oncogene transmembrane protein 60 is a potential therapeutic target in gliomaFengdong YangXuezhi ZhangXinzhuang WangYake XueXianzhi LiuGlioma is a malignant tumor with a high fatality rate, originating in the central nervous system. Even after standard treatment, the prognosis remains unsatisfactory, probably due to the lack of effective therapeutic targets. The family of transmembrane proteins (TMEM) is a large family of genes that encode proteins closely related to the malicious behavior of tumors. Thus, it is necessary to explore the molecular and clinical characteristics of newly identified oncogenes, such as transmembrane protein 60 (TMEM60), to develop effective treating options for glioma. We used bioinformatic methods and basic experiments to verify the expression of transmembrane protein 60 in gliomas and its relationship with 1p and 19q (1p19q) status, isocitrate dehydrogenase (IDH) status, patient prognosis, and immune cell infiltration using public databases and clinical samples. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to detect co-expressed genes. Thus, we inhibited the expression of transmembrane protein 60 to observe the proliferation and activity of glioma LN229 cells. We found transmembrane protein 60 was significantly upregulated in glioma compared with that in normal brain tissue at the mRNA. In the subgroups of World Health Organization high grade, isocitrate dehydrogenase wildtype, 1p and 19q non-codeletion, or isocitrate dehydrogenase wild combined with 1p and 19q non-codeletion, the expression of transmembrane protein 60 increased, and the prognosis of glioma patients worsened. In the transmembrane protein 60 high expression group, infiltration of immune cells and stromal cells in the tumor microenvironment increased, tumor purity decreased, and immune cells and pathways were activated. The immune cells mainly included regulatory T-cell, gamma delta T-cell, macrophages M0, neutrophils, and CD8+ T-cells. Overexpression of co-inhibitory receptors (CTLA4, PDL1 and CD96) may promote the increase of depletion of T-cell, thus losing the anti-tumor function in the transmembrane protein 60 high expression group. Finally, we found that transmembrane protein 60 silencing weakened the viability, proliferation, and colony formation of glioma LN229 cells. This is the 0 report on the abnormally high expression of transmembrane protein 60 in glioma and its related clinical features, such as tumor microenvironment, immune response, tumor heterogeneity, and patient prognosis. We also found that transmembrane protein 60 silencing weakened the proliferation and colony formation of glioma LN229 cells. Thus, the new oncogene transmembrane protein 60 might be an effective therapeutic target for the clinical treatment of glioma.https://www.frontiersin.org/articles/10.3389/fgene.2022.1029270/fulltransmembrane protein 60isocitrate dehydrogenase 11p19qgliomabiomarkertumor microenvironment |
| spellingShingle | Fengdong Yang Xuezhi Zhang Xinzhuang Wang Yake Xue Xianzhi Liu The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma Frontiers in Genetics transmembrane protein 60 isocitrate dehydrogenase 1 1p19q glioma biomarker tumor microenvironment |
| title | The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma |
| title_full | The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma |
| title_fullStr | The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma |
| title_full_unstemmed | The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma |
| title_short | The new oncogene transmembrane protein 60 is a potential therapeutic target in glioma |
| title_sort | new oncogene transmembrane protein 60 is a potential therapeutic target in glioma |
| topic | transmembrane protein 60 isocitrate dehydrogenase 1 1p19q glioma biomarker tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1029270/full |
| work_keys_str_mv | AT fengdongyang thenewoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT xuezhizhang thenewoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT xinzhuangwang thenewoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT yakexue thenewoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT xianzhiliu thenewoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT fengdongyang newoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT xuezhizhang newoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT xinzhuangwang newoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT yakexue newoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma AT xianzhiliu newoncogenetransmembraneprotein60isapotentialtherapeutictargetinglioma |