CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer
Abstract Background Ovarian cancer (OC) has high mortality and poor prognosis for lacking of specific biomarkers and typical clinical symptoms in the early stage. CEBPG is an important regulator in tumor development, yet it is unclear exactly how it contributes to the progression of OC. Methods TCGA...
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| Format: | Article |
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BMC
2023-05-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-023-04136-0 |
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| author | Xiaoqian Zhang Xiaocui Zheng Xiang Ying Weiwei Xie Yujia Yin Xipeng Wang |
| author_facet | Xiaoqian Zhang Xiaocui Zheng Xiang Ying Weiwei Xie Yujia Yin Xipeng Wang |
| author_sort | Xiaoqian Zhang |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer (OC) has high mortality and poor prognosis for lacking of specific biomarkers and typical clinical symptoms in the early stage. CEBPG is an important regulator in tumor development, yet it is unclear exactly how it contributes to the progression of OC. Methods TCGA and tissue microarrays with immunohistochemical staining (IHC) were used to examine CEBPG expression in OC. A variety of in vitro assays were conducted, including colony formation, proliferation, migration, and invasion. The orthotopic OC mouse model was established for in vivo studies. Ferroptosis was detected by observing mitochondrial changes with electron microscopy, detecting ROS expression, and detecting cell sensitivity to drugs by CCK8 assay. The interaction between CEBPG and SLC7A11 was confirmed by CUT&Tag and dual luciferase reporter assays. Results A significantly higher expression level of CEBPG in OC when compared with benign tissues of ovary, and that high CEBPG expression level was also tightly associated with poor prognosis of patients diagnosed with OC, as determined by analysis of datasets and patient samples. Conversely, knockdown of CEBPG inhibited OC progression using experiments of OC cell lines and in vivo orthotopic OC-bearing mouse model. Importantly, CEBPG was identified as a new participator mediating ferroptosis evasion in OC cells using RNA-sequencing, which could contribute to OC progression. The CUT&Tag and dua luciferase reporter assays further revealed the inner mechanism that CEBPG regulated OC cell ferroptosis through transcriptional control of SLC7A11. Conclusions Our findings established CEBPG as a novel transcriptional regulator of OC ferroptosis, with potential value in predicting clinical outcomes and as a therapeutic candidate. |
| first_indexed | 2024-03-13T10:12:19Z |
| format | Article |
| id | doaj.art-20d812ed6eab4fc2830f89ca4e771b53 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-13T10:12:19Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-20d812ed6eab4fc2830f89ca4e771b532023-05-21T11:25:39ZengBMCJournal of Translational Medicine1479-58762023-05-0121111510.1186/s12967-023-04136-0CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancerXiaoqian Zhang0Xiaocui Zheng1Xiang Ying2Weiwei Xie3Yujia Yin4Xipeng Wang5Department of Obstetrics and Gynecology, XinHua Hospital, Shanghai JiaoTong University School of MedicineDepartment of Obstetrics and Gynecology, XinHua Hospital, Shanghai JiaoTong University School of MedicineDepartment of Obstetrics and Gynecology, XinHua Hospital, Shanghai JiaoTong University School of MedicineDepartment of Obstetrics and Gynecology, XinHua Hospital, Shanghai JiaoTong University School of MedicineDepartment of Obstetrics and Gynecology, XinHua Hospital, Shanghai JiaoTong University School of MedicineDepartment of Obstetrics and Gynecology, XinHua Hospital, Shanghai JiaoTong University School of MedicineAbstract Background Ovarian cancer (OC) has high mortality and poor prognosis for lacking of specific biomarkers and typical clinical symptoms in the early stage. CEBPG is an important regulator in tumor development, yet it is unclear exactly how it contributes to the progression of OC. Methods TCGA and tissue microarrays with immunohistochemical staining (IHC) were used to examine CEBPG expression in OC. A variety of in vitro assays were conducted, including colony formation, proliferation, migration, and invasion. The orthotopic OC mouse model was established for in vivo studies. Ferroptosis was detected by observing mitochondrial changes with electron microscopy, detecting ROS expression, and detecting cell sensitivity to drugs by CCK8 assay. The interaction between CEBPG and SLC7A11 was confirmed by CUT&Tag and dual luciferase reporter assays. Results A significantly higher expression level of CEBPG in OC when compared with benign tissues of ovary, and that high CEBPG expression level was also tightly associated with poor prognosis of patients diagnosed with OC, as determined by analysis of datasets and patient samples. Conversely, knockdown of CEBPG inhibited OC progression using experiments of OC cell lines and in vivo orthotopic OC-bearing mouse model. Importantly, CEBPG was identified as a new participator mediating ferroptosis evasion in OC cells using RNA-sequencing, which could contribute to OC progression. The CUT&Tag and dua luciferase reporter assays further revealed the inner mechanism that CEBPG regulated OC cell ferroptosis through transcriptional control of SLC7A11. Conclusions Our findings established CEBPG as a novel transcriptional regulator of OC ferroptosis, with potential value in predicting clinical outcomes and as a therapeutic candidate.https://doi.org/10.1186/s12967-023-04136-0CEBPGOvarian cancerFerroptosisSLC7A11 |
| spellingShingle | Xiaoqian Zhang Xiaocui Zheng Xiang Ying Weiwei Xie Yujia Yin Xipeng Wang CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer Journal of Translational Medicine CEBPG Ovarian cancer Ferroptosis SLC7A11 |
| title | CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer |
| title_full | CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer |
| title_fullStr | CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer |
| title_full_unstemmed | CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer |
| title_short | CEBPG suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer |
| title_sort | cebpg suppresses ferroptosis through transcriptional control of slc7a11 in ovarian cancer |
| topic | CEBPG Ovarian cancer Ferroptosis SLC7A11 |
| url | https://doi.org/10.1186/s12967-023-04136-0 |
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