ArticleClinical epigenetics2018
Epigenetic regulation of ID4 in breast cancer: tumor suppressor or oncogene?
Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Upregulated miR‑203a‑3p and its potential molecular mechanism in breast cancer: A study based on bioinformatics analyses and a comprehensive meta‑analysis.Molecular medicine reports · 2018Pooled it
- Helicobacter pylori-induced aberrant methylation of ID4 mediated by DNMT3B drives gastric cancer progression via DEC1-SHH signaling pathway.Cell death & disease · 2025Article
- The Critical Role of Inhibitor of Differentiation 4 in Breast Cancer: From Mammary Gland Development to Tumor Progression.Cancer medicine · 2025Review
- CDC42 as an epigenetic regulator of ID4 in triple-negative breast tumors.Breast cancer (Tokyo, Japan) · 2022Article
- Identification and validation of plasma biomarkers for diagnosis of breast cancer in South Asian women.Scientific reports · 2022Article
- Anti-tumor effects of an ID antagonist with no observed acquired resistance.NPJ breast cancer · 2021Article
- High Expression of PIGC Predicts Unfavorable Survival in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2021Article
- N6-Methyladenosine-Related Long Noncoding RNAs as Potential Prognosis Biomarkers for Endometrial Cancer.International journal of general medicine · 2021Article
- UVB induces cutaneous squamous cell carcinoma progression by de novo ID4 methylation via methylation regulating enzymes.EBioMedicine · 2020Article
- Identification of crucial aberrantly methylated and differentially expressed genes related to cervical cancer using an integrated bioinformatics analysis.Bioscience reports · 2020Article
- An Integrated Autophagy-Related Long Noncoding RNA Signature as a Prognostic Biomarker for Human Endometrial Cancer: A Bioinformatics-Based Approach.BioMed research international · 2020Article
- ID4 Promotes Breast Cancer Chemotherapy Resistance via CBF1-MRP1 Pathway.Journal of Cancer · 2020Article
- Expression and Prognostic Value of Id-4 in Patients with Esophageal Squamous Cell Carcinoma.OncoTargets and therapy · 2020Article
- Article
- Epigenomic dysregulation-mediated alterations of key biological pathways and tumor immune evasion are hallmarks of gingivo-buccal oral cancer.Clinical epigenetics · 2019Article
- Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma.BioMed research international · 2019Article
- MicroRNA-188-5p Promotes Epithelial-Mesenchymal Transition by Targeting ID4 Through Wnt/β‑catenin Signaling in Retinoblastoma.OncoTargets and therapy · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundInhibitor of differentiation protein 4 (ID4) is a dominant negative regulator of the basic helix-loop-helix (bHLH) family of transcription factors. During tumorigenesis, ID4 may act as a tumor suppressor or as an oncogene in different tumor types. However, the role of ID4 in breast cancer is not clear where both an oncogenic and a tumor suppressor function have been attributed. Here, we hypothesize that ID4 behaves as both, but its role in breast differs according to the estrogen receptor (ER) status of the tumor.
methodsID4 expression was retrieved from TCGA database using UCSC Xena. Association between overall survival (OS) and ID4 was assessed using Kaplan-Meier plotter. Correlation between methylation and expression was analyzed using the MEXPRESS tool. In vitro experiments involved ectopic expression of ID4 in MCF-7, T47D, and MDA-MB231 breast cancer cell lines. Migration and colony formation capacity were assessed after transfection treatments. Gene expression was analyzed by ddPCR and methylation by MSP, MS-MLPA, or ddMSP.
resultsData mining analysis revealed that ID4 expression is significantly lower in ER+ tumors with respect to ER- tumors or normal tissue. We also demonstrate that ID4 is significantly methylated in ER+ tumors. Kaplan-Meier analysis indicated that low ID4 expression levels were associated with poor overall survival in patients with ER+ tumors. In silico expression analysis indicated that ID4 was associated with the expression of key genes of the ER pathway only in ER+ tumors. In vitro experiments revealed that ID4 overexpression in ER+ cell lines resulted in decreased migration capacity and reduced number of colonies. ID4 overexpression induced a reduction in ER levels in ER+ cell lines, while estrogen deprivation with fulvestrant did not induce changes neither in ID4 methylation nor in ID4 expression.
conclusionsWe propose that ID4 is frequently silenced by promoter methylation in ER+ breast cancers and functions as a tumor suppressor gene in these tumors, probably due to its interaction with key genes of the ER pathway. Our present study contributes to the knowledge of the role of ID4 in breast cancer.
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