EMX2 is epigenetically silenced and suppresses epithelial‑mesenchymal transition in human esophageal adenocarcinoma

Wang, Lei; Jin, Julia; Zhou, Yong; Tian, Ziqiang; He, Biao; Yan-chun, Huang; Ding, Feng

doi:10.3892/or.2019.7284

Cited by 6 publications

(6 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EMX2 has been shown to inhibit a number of cancer-related pathways, including PI3K/AKT [ 52 ] and Wnt/-catenin [ 53 ]. The Wnt/-catenin pathway is important for normal tissue morphogenesis as well as tumor development, including cervical cancer [ 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

Jiang

Shi

2022

Journal of Healthcare Engineering

View full text Add to dashboard Cite

The goal of this research was to find noval transcription factors (TFs) that are involved in cervical carcinogenesis. The Gene Expression Omnibus (GEO) database was utilized to analyze ten cervical cancer datasets using the Robust Rank Aggregation (RRA) technique. Survival and differential expression were validated using GEPIA (Gene Expression Profiling Interactive Analysis). The transcriptional regulatory network and putative targets were built using Cytoscape. A real-time PCR (quantitative real-time polymerase chain reaction) experiment was used to confirm the mRNA expression. Using public cervical cancer single-cell RNA-sequencing (scRNA-seq), bulk TCGA-CESC RNA-seq, and microarray datasets, coexpression correlations between putative targets and TFs were confirmed. After combining the results of 10 datasets, 8 TFs, including EMX2 (Empty Spiracles Homeobox 2), were chosen among 385 robust DEGs. In the normal female reproductive tract, EMX2 is extensively expressed, but it is reduced in cervical cancer. Overexpression EMX2 suppresses the proliferation of HeLa cells. 12 potential targets of EMX2 were selected. Our research has revealed evidence that EMX2 acted as a tumor suppressor in cervical cancer and PDZRN3 might be possible target of EMX2 in cervical cancer. It might be a therapeutic target in the future.

show abstract

Section: Discussionmentioning

confidence: 99%

“…EMX2 has been shown to inhibit a number of cancerrelated pathways, including PI3K/AKT [52] and Wnt/catenin [53].…”

Section: Discussionmentioning

confidence: 99%

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

Jiang

Shi

2022

Journal of Healthcare Engineering

View full text Add to dashboard Cite

show abstract

“…These results were consistent with the results of a previous study which demonstrated that overexpressing EMX2 inhibits cell migration and invasion via suppressing Akt phosphorylation in esophageal adenocarcinoma cell lines. 29 As previous studies have shown activated Akt regulates the activity and expression of FOXO3a by binding to FOXO3a and regulating its phosphorylation. 15,[30][31][32] We then explored and found that EMX2 can bind with both Akt and FOXO3a.…”

Section: Discussionmentioning

confidence: 96%

EMX2 inhibits clear cell renal cell carcinoma progress via modulating Akt/FOXO3a pathway

Zhou,

Dong,

Zhou

et al. 2024

Molecular Carcinogenesis

View full text Add to dashboard Cite

Empty spiracles homeobox 2 (EMX2) is initially identified as a key transcription factor that plays an essential role in the regulation of neuronal development and some brain disorders. Recently, several studies emphasized that EMX2 could as a tumor suppressor, but its role in human clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we investigated the role and underlying mechanism of EMX2 in the regulation of ccRCC progress. Our results demonstrated that EMX2 expression was markedly decreased in ccRCC tissues and cell lines, and low EMX2 expression predicted the poor prognosis of ccRCC patients. In addition, forced expression of EMX2 significantly inhibited the cell growth, migration, and invasion in vitro, as well as ccRCC tumor growth in nude mice, via, at least in part, regulating Akt/FOXO3a pathway. In detail, EMX2 could attenuate the phosphorylation levels of Akt and FOXO3a, and increase FOXO3a expression without affecting total Akt expression in vivo and in vitro. Meanwhile, shRNA‐mediated knockdown of FOXO3a expression could obviously attenuate the effects of EMX2 on cell growth, migration, invasion, and tumor growth. Furthermore, EMX2 could significantly attenuate the interaction between Akt and FOXO3a. Taken together, our results demonstrated that EMX2 could inhibit ccRCC progress through, at least in part, modulating Akt/FOXO3a signaling pathway, thus representing a novel role and underlying mechanism of EMX2 in the regulation of ccRCC progress.

show abstract

“…Moreover, we found that high methylation silencing of cg14845689 in EXM2 could increase patient's prognostic risk. EXM2 is thought as a tumor suppressor gene, and high expression of EXM2 can induce cell cycle stagnation thereby inhibiting the proliferation of cancer cells [ 46 , 47 ]. SDK1 is a kind of immune-related protein, and studies found that SDK1 mutation causes cancers, but the effect of SDK1-related site methylation on the incidence of cancer has not been fully studied [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Construction of Prognostic Risk Model of Patients with Skin Cutaneous Melanoma Based on TCGA-SKCM Methylation Cohort

Cong

Wei

et al. 2022

Computational and Mathematical Methods in Medicine

Self Cite

View full text Add to dashboard Cite

Skin cutaneous melanoma (SKCM) is a common malignant skin cancer. Early diagnosis could effectively reduce SKCM patient’s mortality to a large extent. We managed to construct a model to examine the prognosis of SKCM patients. The methylation-related data and clinical data of The Cancer Gene Atlas- (TCGA-) SKCM were downloaded from TCGA database. After preprocessing the methylation data, 21,861 prognosis-related methylated sites potentially associated with prognosis were obtained using the univariate Cox regression analysis and multivariate Cox regression analysis. Afterward, unsupervised clustering was used to divide the patients into 4 clusters, and weighted correlation network analysis (WGCNA) was applied to construct coexpression modules. By overlapping the CpG sites between the clusters and turquoise model, a prognostic model was established by LASSO Cox regression and multivariate Cox regression. It was found that 9 methylated sites included cg01447831, cg14845689, cg20895058, cg06506470, cg09558315, cg06373660, cg17737409, cg21577036, and cg22337438. After constructing the prognostic model, the performance of the model was validated by survival analysis and receiver operating characteristic (ROC) curve, and the independence of the model was verified by univariate and multivariate regression. It was represented that the prognostic model was reliable, and riskscore could be used as an independent prognostic factor in SKCM patients. At last, we combined clinical data and patient’s riskscore to establish and testify the nomogram that could determine patient’s prognosis. The results found that the reliability of the nomogram was relatively good. All in all, we constructed a prognostic model that could determine the prognosis of SKCM patients and screened 9 key methylated sites through analyzing data in TCGA-SKCM dataset. Finally, a prognostic nomogram was established combined with clinical diagnosed information and riskscore. The results are significant for improving the prognosis of SKCM patients in the future.

show abstract

EMX2 is epigenetically silenced and suppresses epithelial‑mesenchymal transition in human esophageal adenocarcinoma

Cited by 6 publications

References 54 publications

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

Functional New Transcription Factors (TFs) Associated with Cervical Cancer

EMX2 inhibits clear cell renal cell carcinoma progress via modulating Akt/FOXO3a pathway

Construction of Prognostic Risk Model of Patients with Skin Cutaneous Melanoma Based on TCGA-SKCM Methylation Cohort

Contact Info

Product

Resources

About