Author:
Zhang Xiaoqian,Zheng Xiaocui,Ying Xiang,Xie Weiwei,Yin Yujia,Wang Xipeng
Abstract
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.
Funder
National Natural Science Foundation of China
Program of Shanghai Academic Research Leader
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献