ZBTB7A, a potential biomarker for prognosis and immune infiltrates, inhibits progression of endometrial cancer based on bioinformatics analysis and experiments

Abstract

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. The ZBTB7A has been largely linked to different kinds of tumors due to its diverse function. However, the value for ZBTB7A in uterine corpus endometrial carcinoma (UCEC) is unclear. Methods In our work, we assessed the importance of ZBTB7A 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 ZBTB7A and tumor immune invasion, and to detect the correlation between the ZBTB7A and the marker genes related to immune infiltration. Finally, CCK8, migration, ChIP assays were introduced to partly validate ZBTB7A function in endometrial cancer cells. Results We found the ZBTB7A expression in TIMER was associated with various cancers, especially UCEC. The decreased expression of ZBTB7A was markedly related to the stage and prognosis of UCEC. Furthermore, ZBTB7A was also related to the expression of various immune markers such as Neutrophils, Dendritic cell, T cell (general), Th1, Th2, and Treg. Finally, we verified that ZBTB7A repressed E2F4 transcription and inhibited cells proliferation and migration. These results indicate that ZBTB7A may play a vital role in regulating immune cell infiltration in UCEC, and is a valuable prognostic marker. Conclusions In summary, we demonstrate that ZBTB7A is notably downregulated in UCEC, plays a vital role in regulating immune cell infiltration, possesses diagnostic and prognostic values and attenuates E2F4 transcription and cell proliferation, migration in vitro.

Recent Multiomics Approaches in Endometrial Cancer

“…The reduced ZBTB7A level in endometrial cancer was observed in analyses using the UALCAN and Oncomine databases and was validated with the GEPIA database [49]. In addition, the overexpression of LGR5 and SST in endometrial cancer reported with the Oncomine database was also confirmed with GEPIA.…”

“…Similarly, Geng et al used the Oncomine database to assess the expression of Zinc finger and BTB domain-containing protein 7A (ZBTB7A). Significant reduction in mRNA expression and DNA copy number variation of ZBTB7A was noted in endometrial cancer compared to the control [49]. This is a valuable observation, as ZBTB7A is considered an oncogene that may constitute a potential therapeutic target.…”

“…Expression of TMEFF2 [47] and BTG anti-proliferation factor 1 (BTG1) [50] was lower in primary endometrial cancer compared to the healthy endometrium, while significant overexpression was noted for ring finger protein 183 (RNF183) [48]. In turn, the ZBTB7A expression was low in endometrial cancer tissues grouped according to cancer stage, age, and race compared to the control group [49].…”

“…Similarly for ZBTB7A, approximately 20,000 genes correlated with its expression. The implementation of GSEA allowed selecting the following targets of ZBTB7A: pololike kinase 1 (PLK1), cyclin-dependent kinase 1 (CDK1) and 2 (CDK2), Aurora kinase B (AURKB), tumor-associated macrophages (ATM), miR-212, miR-132, miR-499, miR-202, miR-485-3P, miR-522, and E2F family [49].…”

Analysis of lncRNAs and mRNA Expression in the ZBTB1 Knockout Monoclonal EL4 Cell Line and Combined Analysis With miRNAs and circRNAs

“…The Zbtb1 family consists of a different set of transcription factors, and Zbtb1 plays an important role in lymphocyte development ( Zhu et al., 2018 ). The Zbtb protein family also plays an important role in cancer, such as in the relationship between Zbtb7 and endometrial cancer cells and bladder cancer cells ( Guo et al., 2017 ; Geng et al., 2020 ).…”