Objective As a gate-keeper enzyme link, pyruvate dehydrogenase E1 subunit alpha (PDHA1) functions as a key regulator during glycolysis and the mitochondrial citric acid cycle, which has been reported in several tumors. Nevertheless, the effects of PDHA1 on biological behaviors and metabolism remain unclear in cervical cancer (CC) cells. The study aims to explore the PDHA1 effects on glucose metabolism in CC cells and its possible mechanism. Methods We first determined the expression levels of PDHA1 and activating protein 2 alpha (AP2α) as a PDHA1 potential transcription factor. The effects of PDHA1 in vivo were evaluated through a subcutaneous xenograft mouse model. Cell Counting Kit-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) labeling assay, Transwell invasion assay, wound healing assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometry were performed in CC cells. Oxygen consumption rate (OCR) levels were determined to reflect aerobic glycolysis level in gastric cancer cells. Reactive oxygen species (ROS) level was measured with 2′, 7′-dichlorofluorescein diacetate kit. The relationship between PDHA1 and AP2α was examined by conducting chromatin immunoprecipitation assay and electrophoretic mobility shift assay. Results In CC tissues and cell lines, PDHA1 was downregulated, while AP2α was upregulated. Overexpression of PDHA1 remarkedly inhibited the proliferation, invasion and migration of CC cells, and tumor growth in vivo, as well as promoted OCR, apoptosis and ROS production. Moreover, AP2α directly bound to PDHA1 within suppressor of cytokine signaling 3 promoter region to negatively regulate PDHA1 expression level. What is more, PDHA1 knockdown could effectively reversed the AP2α silencing-mediated suppressive effects on cell proliferation, invasion, migration, and the promotive effects of AP2α knockdown on OCR, apoptosis and ROS production. Conclusions Our findings demonstrate that AP2α negatively regulated PDHA1 via binding to PDHA1 gene promoter to promote malignant CC cell behaviors, which may provide a potential approach for CC therapeutics.
The authors have withdrawn this preprint due to author disagreement.
Backgroud: ZBTB protein is an important member of the C2H2 zinc finger protein family. As a transcription factor, it is widely involved in the transcriptional regulation of genes, cell proliferation, differentiation, and apoptosis. However, the role of ZBTB7A in uterine corpus endometrial carcinoma (UCEC) is unclear.Methods: In our work, we assessed the importance of ZBTB 7A in UCEC. Firstly, Using Oncomine and Tumor Immunoassay Resource (TIMER) databases to evaluate the expression of ZBTB7A. Secondly, we explored the co expression network of ZBTB7A through the cBioPortal online tool, Metascape, and LinkedOmics. TIMER was also used to explore the relationship between ZB TB7A and tumor immu ne invasion, and to detect the correlation between the ZBTB7A and the marker genes related to immune infiltration. Finally, CKK8,migration, ChIP assays were introduced to partly validate ZBTB7A function in endometrialcancer cells.Results: We found t he ZBTB7A expression in TIMER was associated with various cancers, especially UCEC. The decreased expre ssion of ZBTB7A was markedly related to the stage and prognosis of UCEC. Furthermore, ZBTB7A was also related to the expression of various immune markers s uch as Neutrophils, Dendritic cell, T cell (general), Th1, Th2, and Finally, we verified that ZBTB7 A repressed E2F4 transcription and inhibited cell s proliferation and migration . These results indicate that ZBTB7A may play a vital role in regulating immune cellinfiltration in UCEC, and is a valuable prognostic marker.Conclusions:In summary, we demonstrate that ZBTB7A is notably downregulated in UCEC, play s a vital role in regu lating immune cell infiltration, possesses diagnostic and pr ognostic values and attenuated E2F4 transcription and cell proliferation , migration in vitro.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.