GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC
BackgroundTNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1033367/full |
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| author | Huaying Xie Tingting Yan Xinxin Lu Yueyao Du Shuguang Xu Yu Kong Liangjie Yu Jian Sun Liheng Zhou Jun Ma |
| author_facet | Huaying Xie Tingting Yan Xinxin Lu Yueyao Du Shuguang Xu Yu Kong Liangjie Yu Jian Sun Liheng Zhou Jun Ma |
| author_sort | Huaying Xie |
| collection | DOAJ |
| description | BackgroundTNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors involved in regulating the progression of TNBC.MethodsWe analyzed the expression profiles of TNBC in TCGA and the prognoses values of GLDC. Correlations of GLDC and tumor immune infiltration were also identified. CCK8 and BrdU incorporation assays were utilized to determine cell proliferation. The mRNA and protein levels were examined by using Real-time PCR and Western blot analysis.ResultsIn the present study, we analyzed the mRNA expression profiles of TNBC in TCGA and found that GLDC, a key enzyme in glycine cleavage system, was significantly up-regulated in TNBC tissues and higher expression of GLDC was correlated with a worse prognosis in TNBC. Moreover, the expression of GLDC was negatively correlated with macrophage and monocyte and positively correlated with activated CD4 T cell and type 2 T helper cell in TNBC. Overexpression of GLDC facilitated the proliferation of TNBC cells, whereas GLDC knockdown had the opposite effects. Additionally, miR-30e acts as a functional upstream regulator of GLDC and the inhibitory effects of miR-30e on cell proliferation were mitigated by the reintroduction of GLDC.ConclusionsThese results imply that miR-30e-depressed GLDC acts as a tumor suppressive pathway in TNBC and provides potential targets for the treatment of TNBC. |
| first_indexed | 2024-04-12T09:34:31Z |
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| id | doaj.art-9cca67cd04c442239b904ba24966df72 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T09:34:31Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9cca67cd04c442239b904ba24966df722022-12-22T03:38:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10333671033367GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBCHuaying Xie0Tingting Yan1Xinxin Lu2Yueyao Du3Shuguang Xu4Yu Kong5Liangjie Yu6Jian Sun7Liheng Zhou8Jun Ma9Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Breast Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Oncology, Ganzhou Women and Children’s Health Care Hospital, Ganzhou, ChinaDepartment of Breast Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Breast Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Breast Surgery, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, ChinaDepartment of Breast Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, ChinaEye Institute, Eye & Ear, Nose, and Throat (ENT) Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaBackgroundTNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors involved in regulating the progression of TNBC.MethodsWe analyzed the expression profiles of TNBC in TCGA and the prognoses values of GLDC. Correlations of GLDC and tumor immune infiltration were also identified. CCK8 and BrdU incorporation assays were utilized to determine cell proliferation. The mRNA and protein levels were examined by using Real-time PCR and Western blot analysis.ResultsIn the present study, we analyzed the mRNA expression profiles of TNBC in TCGA and found that GLDC, a key enzyme in glycine cleavage system, was significantly up-regulated in TNBC tissues and higher expression of GLDC was correlated with a worse prognosis in TNBC. Moreover, the expression of GLDC was negatively correlated with macrophage and monocyte and positively correlated with activated CD4 T cell and type 2 T helper cell in TNBC. Overexpression of GLDC facilitated the proliferation of TNBC cells, whereas GLDC knockdown had the opposite effects. Additionally, miR-30e acts as a functional upstream regulator of GLDC and the inhibitory effects of miR-30e on cell proliferation were mitigated by the reintroduction of GLDC.ConclusionsThese results imply that miR-30e-depressed GLDC acts as a tumor suppressive pathway in TNBC and provides potential targets for the treatment of TNBC.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1033367/fullTNBCGLDCproliferationmiR-30etumor immune |
| spellingShingle | Huaying Xie Tingting Yan Xinxin Lu Yueyao Du Shuguang Xu Yu Kong Liangjie Yu Jian Sun Liheng Zhou Jun Ma GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC Frontiers in Immunology TNBC GLDC proliferation miR-30e tumor immune |
| title | GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC |
| title_full | GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC |
| title_fullStr | GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC |
| title_full_unstemmed | GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC |
| title_short | GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC |
| title_sort | gldc mitigated by mir 30e regulates cell proliferation and tumor immune infiltration in tnbc |
| topic | TNBC GLDC proliferation miR-30e tumor immune |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1033367/full |
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