{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:31:48Z","timestamp":1788571908500,"version":"build-2803163510"},"reference-count":182,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Warsaw University of Technology within the Excellence Initiative: Research University (IDUB) program and co-supported by Polish National Science Centre","award":["2020\/37\/B\/NZ2\/03757"],"award-info":[{"award-number":["2020\/37\/B\/NZ2\/03757"]}]},{"name":"Warsaw University of Technology within the Excellence Initiative: Research University (IDUB) program and co-supported by Polish National Science Centre","award":["7054\/IA\/SP\/2020"],"award-info":[{"award-number":["7054\/IA\/SP\/2020"]}]},{"name":"Warsaw University of Technology within the Excellence Initiative: Research University (IDUB) program and co-supported by Polish National Science Centre","award":["1U54DK107967-01"],"award-info":[{"award-number":["1U54DK107967-01"]}]},{"name":"Polish Ministry of Science and Higher Education","award":["2020\/37\/B\/NZ2\/03757"],"award-info":[{"award-number":["2020\/37\/B\/NZ2\/03757"]}]},{"name":"Polish Ministry of Science and Higher Education","award":["7054\/IA\/SP\/2020"],"award-info":[{"award-number":["7054\/IA\/SP\/2020"]}]},{"name":"Polish Ministry of Science and Higher Education","award":["1U54DK107967-01"],"award-info":[{"award-number":["1U54DK107967-01"]}]},{"name":"National Institute of Health USA 4DNucleome","award":["2020\/37\/B\/NZ2\/03757"],"award-info":[{"award-number":["2020\/37\/B\/NZ2\/03757"]}]},{"name":"National Institute of Health USA 4DNucleome","award":["7054\/IA\/SP\/2020"],"award-info":[{"award-number":["7054\/IA\/SP\/2020"]}]},{"name":"National Institute of Health USA 4DNucleome","award":["1U54DK107967-01"],"award-info":[{"award-number":["1U54DK107967-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer affects over 2 million women annually and results in 650,000 deaths. This study aimed to identify epigenetic mechanisms impacting breast cancer-related gene expression, discover potential biomarkers, and present a novel approach integrating feature selection, Natural Language Processing, and 3D chromatin structure analysis. We used The Cancer Genome Atlas database with over 800 samples and multi-omics datasets (mRNA, miRNA, DNA methylation) to select 2701 features statistically significant in cancer versus control samples, from an initial 417,486, using the Monte Carlo Feature Selection and Interdependency Discovery algorithm. Classification of cancer vs. control samples on the selected features returned very high accuracy, depending on feature-type and classifier. The cancer samples generally showed lower expression of differentially expressed genes (DEGs) and increased \u03b2-values of differentially methylated sites (DMSs). We identified mRNAs whose expression is explained by miRNA expression and \u03b2-values of DMSs. We recognized DMSs affecting NRF1 and MXI1 transcription factors binding, causing a disturbance in NKAPL and PITX1 expression, respectively. Our 3D models showed more loosely packed chromatin in cancer. This study highlights numerous possible regulatory dependencies, and the presented bioinformatic approach provides a robust framework for data dimensionality reduction, enabling the identification of key features for further experimental validation.<\/jats:p>","DOI":"10.3390\/ijms26146558","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T07:31:57Z","timestamp":1751959917000},"page":"6558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling Epigenetic Regulatory Elements Associated with Breast Cancer Development"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-6266","authenticated-orcid":false,"given":"Marta","family":"Jardanowska-Kotuniak","sequence":"first","affiliation":[{"name":"Computational Biology Group, Institute of Computer Science of the Polish Academy of Sciences, 01-248 Warsaw, Poland"},{"name":"Institute of Biochemistry and Biophysics of the Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Drami\u0144ski","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Institute of Computer Science of the Polish Academy of Sciences, 01-248 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-0713","authenticated-orcid":false,"given":"Michal","family":"Wlasnowolski","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Computational Genomics, Faculty of Mathematics and Information Science, Warsaw University of Technology, 00-662 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"\u0141api\u0144ski","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Institute of Computer Science of the Polish Academy of Sciences, 01-248 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0603-0916","authenticated-orcid":false,"given":"Kaustav","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Computational Genomics, Faculty of Mathematics and Information Science, Warsaw University of Technology, 00-662 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4981-8746","authenticated-orcid":false,"given":"Abhishek","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Laboratory of Functional and Structural Genomics, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Filip","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Institute of Computer Science of the Polish Academy of Sciences, 01-248 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimisha","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, Shiv Nadar University, Chennai 201314, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-624X","authenticated-orcid":false,"given":"Vera","family":"Pancaldi","sequence":"additional","affiliation":[{"name":"Cancer Research Center Toulouse, National Centre for Scientific Research (CNRS), Inserm, Universit\u00e9 de Toulouse, 31037 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Grynberg","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics of the Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-9707","authenticated-orcid":false,"given":"Indrajit","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, National Institute of Technical Teachers\u2019 Training and Research, Kolkata 700106, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3840-7610","authenticated-orcid":false,"given":"Dariusz","family":"Plewczynski","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Computational Genomics, Faculty of Mathematics and Information Science, Warsaw University of Technology, 00-662 Warsaw, Poland"},{"name":"Laboratory of Functional and Structural Genomics, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1269-6722","authenticated-orcid":false,"given":"Micha\u0142 J.","family":"D\u0105browski","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Institute of Computer Science of the Polish Academy of Sciences, 01-248 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a001578","DOI":"10.1101\/mcs.a001578","article-title":"Personalized cancer therapy\u2014Leveraging a knowledge base for clinical decision-making","volume":"4","author":"Dumbrava","year":"2018","journal-title":"Mol. Case Stud."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chopra, S., Khosla, M., and Vidya, R. (2023). Innovations and challenges in breast cancer care: A review. Medicina, 59.","DOI":"10.3390\/medicina59050957"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.mpdhp.2021.01.001","article-title":"Breast neuroendocrine neoplasms: Practical applications and continuing challenges in the era of the 5th edition of the WHO classification of breast tumours","volume":"27","author":"Bean","year":"2021","journal-title":"Diagn. Histopathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/his.13977","article-title":"Revising the WHO classification: Female genital tract tumours","volume":"76","author":"Cree","year":"2019","journal-title":"Histopathology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1145\/76359.76371","article-title":"Learnability and the Vapnik-Chervonenkis dimension","volume":"36","author":"Blumer","year":"1989","journal-title":"J. ACM"},{"key":"ref_7","first-page":"1","article-title":"rmcfs: An R Package for Monte Carlo Feature Selection and Interdependency Discovery","volume":"85","author":"Koronacki","year":"2018","journal-title":"J. Stat. Softw."},{"key":"ref_8","first-page":"285","article-title":"Discovering networks of interdependent features in high-dimensional problems","volume":"Volume 16","author":"Japkowicz","year":"2015","journal-title":"Big Data Analysis: New Algorithms for a New Society. Studies in Big Data"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chen, L., Zhou, X., Zeng, T., Pan, X., Zhang, Y.H., Huang, T., Fang, Z., and Cai, Y.D. (2021). Recognizing pattern and rule of mutation signatures corresponding to cancer types. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.712931"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, J., Xu, Q., Wu, M., Huang, T., and Wang, Y. (2020). Pan-cancer classification based on self-normalizing neural networks and feature selection. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00766"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, Z., Mei, Z., Ding, S., Chen, L., Li, H., Feng, K., Huang, T., and Cai, Y.D. (2022). Identifying methylation signatures and rules for COVID-19 with machine learning methods. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.908080"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41434-018-0051-6","article-title":"HIV infection alters the human epigenetic landscape","volume":"26","author":"Chen","year":"2018","journal-title":"Gene Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, D., Lin, H., and Li, L. (2020). Multiple feature selection strategies identified novel cardiac gene expression signature for heart failure. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.604241"},{"key":"ref_14","first-page":"1","article-title":"Emerging role of genomic rearrangements in breast cancer: Applying knowledge from other cancers","volume":"8","author":"Paratala","year":"2016","journal-title":"Biomark. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nature11154","article-title":"Sequence analysis of mutations and translocations across breast cancer subtypes","volume":"486","author":"Banerji","year":"2012","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/bfgp\/elx018","article-title":"Epigenetic regulation of gene expression in cancer: Techniques; resources and analysis","volume":"17","author":"Kagohara","year":"2017","journal-title":"Brief. Funct. Genom."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"D\u0105browski, M.J., Drami\u0144ski, M., Diamanti, K., St\u0119pniak, K., Mozolewska, M.A., Teisseyre, P., Koronacki, J., Komorowski, J., Kaminska, B., and Wojtas, B. (2018). Unveiling new interdependencies between significant DNA methylation sites; gene expression profiles and glioma patients survival. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22829-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.trecan.2020.02.003","article-title":"Cancer epigenetics; tumor immunity; and immunotherapy","volume":"6","author":"Cao","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9260","DOI":"10.18632\/aging.103202","article-title":"Integrative analysis of genomic and epigenetic regulation of endometrial cancer","volume":"12","author":"Zhong","year":"2020","journal-title":"Aging"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Vezzani, B., Carinci, M., Previati, M., Giacovazzi, S., Della Sala, M., Gaf\u00e0, R., Lanza, G., Wieckowski, M.R., Pinton, P., and Giorgi, C. (2022). Epigenetic regulation: A link between inflammation and carcinogenesis. Cancers, 14.","DOI":"10.3390\/cancers14051221"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/nbt.1685","article-title":"Epigenetic modifications and human disease","volume":"28","author":"Portela","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1042\/EBC20190037","article-title":"The DNA methylation landscape in cancer","volume":"63","author":"Skvortsova","year":"2019","journal-title":"Essays Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2217\/epi.15.84","article-title":"Epigenome-based personalized medicine in human cancer","volume":"8","author":"Yan","year":"2016","journal-title":"Epigenomics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1042\/EBC20190033","article-title":"Sensitivity of transcription factors to DNA methylation","volume":"63","author":"Bardet","year":"2019","journal-title":"Essays Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"34287","DOI":"10.1074\/jbc.R113.512517","article-title":"Cross-talk between site-specific transcription factors and DNA methylation states","volume":"288","author":"Blattler","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cancergencyto.2005.07.023","article-title":"SATR-1 hypomethylation is a common and early event in breast cancer","volume":"165","author":"Costa","year":"2006","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20751","DOI":"10.18632\/oncotarget.10612","article-title":"Overexpression of NSUN2 by DNA hypomethylation is associated with metastatic progression in human breast cancer","volume":"8","author":"Yi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1093\/carcin\/bgp143","article-title":"Association between global DNA hypomethylation in leukocytes and risk of breast cancer","volume":"30","author":"Choi","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1245\/ASO.2005.04.010","article-title":"Expression of the transcription factors Snail; Slug; and Twist and their clinical significance in human breast cancer","volume":"12","author":"Martin","year":"2005","journal-title":"Ann. Surg. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6189","DOI":"10.1158\/1078-0432.CCR-04-0597","article-title":"Tumor suppressor gene promoter hypermethylation in serum of breast cancer patients","volume":"10","author":"Dulaimi","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/mc.21881","article-title":"Silencing of tumor suppressor genes RASSF1A.; SLIT2; and WIF1 by promoter hypermethylation in hereditary breast cancer","volume":"52","author":"Alvarez","year":"2012","journal-title":"Mol. Carcinog."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Su, J., Huang, Y.H., Cui, X., Wang, X., Zhang, X., Lei, Y., Xu, J., Lin, X., Chen, K., and Lv, J. (2018). Homeobox oncogene activation by pan-cancer DNA hypermethylation. Genome Biol., 19.","DOI":"10.1186\/s13059-018-1492-3"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1176935119828776","DOI":"10.1177\/1176935119828776","article-title":"Correlation patterns between DNA methylation and gene expression in the cancer genome atlas","volume":"18","author":"Spainhour","year":"2019","journal-title":"Cancer Inform."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cbpa.2019.01.024","article-title":"The roles of microRNAs in epigenetic regulation","volume":"51","author":"Yao","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s12033-007-9013-8","article-title":"The microRNA (miRNA): Overview of the RNA genes that modulate gene function","volume":"38","author":"Ying","year":"2008","journal-title":"Mol. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pavl\u00edkov\u00e1, L., \u0160ere\u0161, M., Breier, A., and Sulov\u00e1, Z. (2022). The roles of microRNAs in cancer multidrug resistance. Cancers, 14.","DOI":"10.3390\/cancers14041090"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz, J.P., P\u00e9rez-Moreno, P., P\u00e9rez, Y., and Calaf, G.M. (2023). The role of microRNAs in breast cancer and the challenges of their clinical application. Diagnostics, 13.","DOI":"10.3390\/diagnostics13193072"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/humu.23014","article-title":"A significant regulatory mutation burden at a high-affinity position of the CTCF motif in gastrointestinal cancers","volume":"37","author":"Umer","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41594-024-01241-6","article-title":"The impact of DNA methylation on CTCF-mediated 3D genome organization","volume":"31","author":"Noordermeer","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15668","DOI":"10.1038\/s41598-021-95009-3","article-title":"The role of epigenetic modifications; long-range contacts; enhancers and topologically associating domains in the regulation of glioma grade-specific genes","volume":"11","author":"Grabowicz","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"32509","DOI":"10.18632\/oncotarget.5085","article-title":"The search for cis-regulatory driver mutations in cancer genomes","volume":"6","author":"Poulos","year":"2015","journal-title":"Oncotarget"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1093\/bioinformatics\/btv635","article-title":"CAMUR: Knowledge extraction from RNA-seq cancer data through equivalent classification rules","volume":"32","author":"Cestarelli","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s10120-018-0866-2","article-title":"ADAMTS5 acts as a tumor suppressor by inhibiting migration; invasion and angiogenesis in human gastric cancer","volume":"22","author":"Huang","year":"2018","journal-title":"Gastric Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/1354750X.2016.1201542","article-title":"MAL and TMEM220 are novel DNA methylation markers in human gastric cancer","volume":"22","author":"Choi","year":"2016","journal-title":"Biomarkers"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2147\/JHC.S298554","article-title":"ARHGAP20 Expression inhibited HCC progression by regulating the PI3K-AKT signaling pathway","volume":"8","author":"Liu","year":"2021","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.7150\/ijbs.41587","article-title":"Development and validation of a prognostic nomogram for gastric cancer based on DNA methylation-driven differentially expressed genes","volume":"16","author":"Bai","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6280","DOI":"10.1002\/jcp.26513","article-title":"Extracellular matrix proteins as diagnostic markers of breast carcinoma","volume":"233","author":"Giussani","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3892\/or.2021.7967","article-title":"MMP11 promotes the proliferation and progression of breast cancer through stabilizing Smad2 protein","volume":"45","author":"Zhuang","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1073\/pnas.1514663113","article-title":"SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis","volume":"113","author":"Ozturk","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Nema, R., and Kumar, A. (2021). Sphingosine-1-phosphate catabolizing enzymes predict better prognosis in triple-negative breast cancer patients and correlates with tumor-infiltrating immune cells. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.697922"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhang, W., Wang, H., Qi, Y., Li, S., and Geng, C. (2022). Epigenetic study of early breast cancer (EBC) based on DNA methylation and gene integration analysis. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-05486-3"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bao, Y., Wang, L., Shi, L., Yun, F., Liu, X., Chen, Y., Chen, C., Ren, Y., and Jia, Y. (2019). Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer. Cell. Mol. Biol. Lett., 24.","DOI":"10.1186\/s11658-019-0162-0"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"D687","DOI":"10.1093\/nar\/gkab1028","article-title":"The reactome pathway knowledgebase 2022","volume":"50","author":"Gillespie","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1007\/s10620-018-4929-3","article-title":"Hypermethylation of NF-\u03baB-Activating Protein-Like (NKAPL) promoter in hepatocellular carcinoma suppresses Its expression and predicts a poor prognosis","volume":"63","author":"Ng","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.humpath.2016.11.001","article-title":"Role of miR-139 as a surrogate marker for tumor aggression in breast cancer","volume":"61","author":"Dai","year":"2016","journal-title":"Hum. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"591","DOI":"10.18632\/oncotarget.28641","article-title":"Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties","volume":"15","author":"Halim","year":"2024","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wang, H., Tan, Z., Hu, H., Liu, H., Wu, T., Zheng, C., Wang, X., Luo, Z., Wang, J., and Liu, S. (2019). microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5951-3"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mohammaddoust, S., and Sadeghizadeh, M. (2023). Mir-183 functions as an oncogene via decreasing PTEN in breast cancer cells. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-35059-x"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Hajibabaei, S., Sotoodehnejadnematalahi, F., Nafissi, N., Zeinali, S., and Azizi, M. (2023). Aberrant promoter hypermethylation of miR-335 and miR-145 is involved in breast cancer PD-L1 overexpression. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-27415-8"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.3389\/fonc.2019.01473","article-title":"MicroRNA-99a Suppresses Breast Cancer Progression by Targeting FGFR3","volume":"9","author":"Long","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s12935-023-02972-0","article-title":"The emerging role of MicroRNA-182 in tumorigenesis; a promising therapeutic target","volume":"23","author":"Sameti","year":"2023","journal-title":"Cancer Cell Int."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Hong, Y., Liang, H., Urrehman, U., Wang, Y., Zhang, W., Zhou, Y., Chen, S., Yu, M., Cui, S., and Liu, M. (2016). miR-96 promotes cell proliferation, migration and invasion by targeting PTPN9 in breast cancer. Sci. Rep., 6.","DOI":"10.1038\/srep37421"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100643","DOI":"10.1016\/j.mgene.2019.100643","article-title":"miR-486-5p regulates cell proliferation and migration in breast cancer","volume":"23","author":"Gharehdaghchi","year":"2019","journal-title":"Meta Gene"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/cam4.1024","article-title":"Downregulation of miRNA-141 in breast cancer cells is associated with cell migration and invasion: Involvement of ANP32E targeting","volume":"6","author":"Li","year":"2017","journal-title":"Cancer Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1056\/NEJMoa2114663","article-title":"Overall survival with ribociclib plus letrozole in advanced breast cancer","volume":"386","author":"Hortobagyi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Tolaney, S.M., Beeram, M., Beck, J.T., Conlin, A., Dees, E.C., Puhalla, S.L., Rexer, B.N., Burris, H.A., Jhaveri, K., and Helsten, T. (2022). Abemaciclib in combination with endocrine therapy for patients with hormone receptor-positive; HER2-negative metastatic breast cancer: A phase 1b study. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.810023"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.trecan.2016.11.008","article-title":"Targeting TGF-\u03b2 Signaling in Cancer","volume":"3","author":"Colak","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1593\/neo.81178","article-title":"The story of human cytomegalovirus and cancer: Increasing evidence and open questions","volume":"11","author":"Michaelis","year":"2009","journal-title":"Neoplasia"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zhao, J., and Xu, Y. (2023). PITX1 plays essential functions in cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1253238"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41523-019-0142-6","article-title":"Androgen receptor gene expression in primary breast cancer","volume":"5","author":"Vidula","year":"2019","journal-title":"npj Breast Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Fallah, Y., Brundage, J., Allegakoen, P., and Shajahan-Haq, A.N. (2017). MYC-driven pathways in breast cancer subtypes. Biomolecules, 7.","DOI":"10.3390\/biom7030053"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"R485","DOI":"10.1530\/ERC-16-0190","article-title":"Androgen receptor signaling pathways as a target for breast cancer treatment","volume":"23","author":"Pietri","year":"2016","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s10911-010-9172-2","article-title":"ErbB\/EGF signaling and EMT in mammary development and breast cancer","volume":"15","author":"Hardy","year":"2010","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mce.2019.02.001","article-title":"Emerging roles for the relaxin\/RXFP1 system in cancer therapy","volume":"487","author":"Thanasupawat","year":"2019","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1007\/s12257-021-0019-z","article-title":"miR-182-5p Inhibits NKAPL expression and Promotes the Proliferation of Osteosarcoma","volume":"26","author":"Yang","year":"2021","journal-title":"Biotechnol. Bioprocess Eng."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1002\/cbin.11406","article-title":"ABCC9; NKAPL; and TMEM132C are potential diagnostic and prognostic markers in triple-negative breast cancer","volume":"44","author":"Zhang","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/ijc.34496","article-title":"Unveiling the epigenomic mechanisms of acquired platinum-resistance in high-grade serous ovarian cancer","volume":"153","author":"Silva","year":"2023","journal-title":"Int. J. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Morales-Mart\u00ednez, M., and Vega, M.I. (2022). Role of MicroRNA-7 (MiR-7) in Cancer Physiopathology. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169091"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3880","DOI":"10.1093\/nar\/gkq126","article-title":"Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns","volume":"38","author":"Schneider","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0092-8674(88)90479-5","article-title":"DNA methylation and gene activity","volume":"53","author":"Cedar","year":"1988","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"W288","DOI":"10.1093\/nar\/gkw437","article-title":"3D-GNOME: An integrated web service for structural modeling of the 3D genome","volume":"44","author":"Szalaj","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"W170","DOI":"10.1093\/nar\/gkaa388","article-title":"3D-GNOME 2.0: A three-dimensional genome modeling engine for predicting structural variation-driven alterations of chromatin spatial structure in the human genome","volume":"48","author":"Wlasnowolski","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41586-020-2151-x","article-title":"Landscape of cohesin-mediated chromatin loops in the human genome","volume":"583","author":"Grubert","year":"2020","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/j.cell.2016.09.037","article-title":"Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters","volume":"167","author":"Javierre","year":"2016","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Beesley, J., Sivakumaran, H., Moradi Marjaneh, M., Lima, L.G., Hillman, K.M., Kaufmann, S., Tuano, N., Hussein, N., Ham, S., and Mukhopadhyay, P. (2020). Chromatin interactome mapping at 139 independent breast cancer risk signals. Genome Biol., 21.","DOI":"10.1186\/s13059-019-1877-y"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/s41594-023-01181-7","article-title":"The potential of epigenetic therapy to target the 3D epigenome in endocrine-resistant breast cancer","volume":"31","author":"Stirzaker","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ymeth.2019.11.014","article-title":"Spring Model\u2014Chromatin modeling tool based on OpenMM","volume":"181\u2013182","author":"Kadlof","year":"2020","journal-title":"Methods"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Mei, J., Zhao, J., and Fu, Y. (2020). Molecular classification of breast cancer using the mRNA expression profiles of immune-related genes. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-61710-y"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Deng, J.L., Xu, Y., and Wang, G. (2019). Identification of potential crucial genes and key pathways in breast cancer using bioinformatic analysis. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00695"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1038\/s41467-018-05429-5","article-title":"Plk1 overexpression induces chromosomal instability and suppresses tumor development","volume":"9","author":"Venkateswaran","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/his.14960","article-title":"Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer","volume":"83","author":"Lashen","year":"2023","journal-title":"Histopathology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.pathol.2019.11.008","article-title":"Decreased Nek9 expression correlates with aggressive behaviour and predicts unfavourable prognosis in breast cancer","volume":"52","author":"Xu","year":"2020","journal-title":"Pathology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.bbamcr.2014.12.036","article-title":"The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis","volume":"1853","author":"Lesko","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s12263-009-0154-1","article-title":"Acetaldehyde as an underestimated risk factor for cancer development: Role of genetics in ethanol metabolism","volume":"5","author":"Seitz","year":"2010","journal-title":"Genes Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/mco2.27","article-title":"Lipid metabolism in cancer progression and therapeutic strategies","volume":"2","author":"Fu","year":"2020","journal-title":"MedComm."},{"key":"ref_98","first-page":"778","article-title":"Lipid metabolism and carcinogenesis; cancer development","volume":"8","author":"Long","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Chen, M.C., Hsu, S.L., Lin, H., and Yang, T.Y. (2014). Retinoic acid and cancer treatment. BioMedicine, 4.","DOI":"10.7603\/s40681-014-0022-1"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"104156","DOI":"10.1016\/j.critrevonc.2023.104156","article-title":"Targeting breast cancer stem cells through retinoids: A new hope for treatment","volume":"192","author":"Jan","year":"2023","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Costantini, L., Molinari, R., Farinon, B., and Merendino, N. (2020). Retinoic acids in the treatment of most lethal solid cancers. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020360"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.7150\/thno.81403","article-title":"Exploring neurotransmitters and their receptors for breast cancer prevention and treatment","volume":"13","author":"Li","year":"2023","journal-title":"Theranostics"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature08144","article-title":"The structure and function of G-protein-coupled receptors","volume":"459","author":"Rosenbaum","year":"2009","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrc2069","article-title":"G-protein-coupled receptors and cancer","volume":"7","author":"Dorsam","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"De Francesco, E., Sotgia, F., Clarke, R., Lisanti, M., and Maggiolini, M. (2017). G Protein-Coupled receptors at the crossroad between physiologic and pathologic angiogenesis: Old paradigms and emerging concepts. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122713"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ejphar.2015.05.011","article-title":"Role and therapeutic potential of G-protein coupled receptors in breast cancer progression and metastases","volume":"763","author":"Singh","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Lappano, R., Jacquot, Y., and Maggiolini, M. (2018). GPCR modulation in breast cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123840"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"He, J., Fortunati, E., Liu, D.X., and Yan, L. (2021). Pleiotropic roles of ABC transporters in breast cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063199"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.canlet.2019.01.010","article-title":"Small molecule BKM1972 inhibits human prostate cancer growth and overcomes docetaxel resistance in intraosseous models","volume":"446","author":"Chen","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"253","DOI":"10.20892\/j.issn.2095-3941.2019.0284","article-title":"ABC transporters and the hallmarks of cancer: Roles in cancer aggressiveness beyond multidrug resistance","volume":"17","author":"Muriithi","year":"2020","journal-title":"Cancer Biol. Med."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Demidenko, R., Razanauskas, D., Daniunaite, K., Lazutka, J.R., Jankevicius, F., and Jarmalaite, S. (2015). Frequent down-regulation of ABC transporter genes in prostate cancer. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1689-8"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.3892\/or.2016.4599","article-title":"Gene expression of membrane transporters: Importance for prognosis and progression of ovarian carcinoma","volume":"35","author":"Elsnerova","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/tox.23495","article-title":"ABCA8 inhibits breast cancer cell proliferation by regulating the AMP activated protein kinase\/mammalian target of rapamycin signaling pathway","volume":"37","author":"Lv","year":"2022","journal-title":"Environ. Toxicol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/10428194.2021.1973672","article-title":"Artificial intelligence models in chronic lymphocytic leukemia\u2014Recommendations toward state-of-the-art","volume":"63","author":"Agius","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.drup.2012.01.008","article-title":"Epigenetic mechanisms in tumorigenesis; tumor cell heterogeneity and drug resistance","volume":"15","author":"Wilting","year":"2012","journal-title":"Drug Resist. Updates"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Ma, L., Li, C., Yin, H., Huang, J., Yu, S., Zhao, J., Tang, Y., Yu, M., Lin, J., and Ding, L. (2023). The mechanism of DNA methylation and miRNA in breast cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119360"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1080\/15384047.2015.1070980","article-title":"KIFC1 is a novel potential therapeutic target for breast cancer","volume":"16","author":"Li","year":"2015","journal-title":"Cancer Biol. Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"48656","DOI":"10.18632\/oncotarget.8799","article-title":"KIFC1: A promising chemotherapy target for cancer treatment?","volume":"7","author":"Xiao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/jcmm.16090","article-title":"HN1L promotes migration and invasion of breast cancer by up-regulating the expression of HMGB1","volume":"25","author":"Jiao","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nature16462","article-title":"Competition between DNA methylation and transcription factors determines binding of NRF1","volume":"528","author":"Domcke","year":"2015","journal-title":"Nature"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1038\/s41467-023-39551-w","article-title":"Dissecting the roles of MBD2 isoforms and domains in regulating NuRD complex function during cellular differentiation","volume":"14","author":"Schmolka","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1056\/NEJM199811263392207","article-title":"Tamoxifen in the treatment of breast cancer","volume":"339","author":"Osborne","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e00726","DOI":"10.7554\/eLife.00726","article-title":"DNA methylation presents distinct binding sites for human transcription factors","volume":"2","author":"Hu","year":"2013","journal-title":"eLife"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrg.2016.83","article-title":"Transcription factors as readers and effectors of DNA methylation","volume":"17","author":"Zhu","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.biocel.2016.01.006","article-title":"Cross-talk between EPAS-1\/HIF-2\u03b1 and PXR signaling pathway regulates multi-drug resistance of stomach cancer cell","volume":"72","author":"Zhao","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e18361","DOI":"10.1111\/jcmm.18361","article-title":"EPAS1; a hypoxia- and ferroptosis-related gene; promotes malignant behaviour of cervical cancer by ceRNA and super-enhancer","volume":"28","author":"Lu","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"6041","DOI":"10.1074\/jbc.M210361200","article-title":"LOT1 (PLAGL1\/ZAC1); the candidate tumor suppressor gene at chromosome 6q24\u201325; is epigenetically regulated in cancer","volume":"278","author":"Abdollahi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e724","DOI":"10.1038\/cddis.2013.235","article-title":"DAX-1; as an androgen-target gene; inhibits aromatase expression: A novel mechanism blocking estrogen-dependent breast cancer cell proliferation","volume":"4","author":"Lanzino","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1002\/jso.21861","article-title":"Expression of nuclear receptor DAX-1 and androgen receptor in human breast cancer","volume":"103","author":"Chae","year":"2011","journal-title":"J. Surg. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1111\/jcmm.15033","article-title":"BHLHE41 suppresses MCF-7 cell invasion via MAPK\/JNK pathway","volume":"24","author":"Zhang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrc3183","article-title":"HIF1\u03b1 and HIF2\u03b1: Sibling rivalry in hypoxic tumor growth and progression","volume":"12","author":"Keith","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Okuda, H., Kiuchi, H., Takao, T., Miyagawa, Y., Tsujimura, A., Nonomura, N., Miyata, H., Okabe, M., Ikawa, M., and Kawakami, Y. (2015). A novel transcriptional factor Nkapl is a germ cell-specific suppressor of notch signaling and is indispensable for spermatogenesis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124293"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"34534","DOI":"10.18632\/oncotarget.15837","article-title":"Transcriptional landscape of human cancers","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/35006129","article-title":"Betaglycan binds inhibin and can mediate functional antagonism of activin signalling","volume":"404","author":"Lewis","year":"2000","journal-title":"Nature"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e935515","DOI":"10.12659\/MSM.935515","article-title":"Identification of key genes and key pathways in breast cancer based on machine learning","volume":"28","author":"Bao","year":"2022","journal-title":"Med. Sci. Monit."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1172\/JCI29293","article-title":"The type III TGF-\u03b2 receptor suppresses breast cancer progression","volume":"117","author":"Dong","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/0962-8924(93)90194-6","article-title":"Signalling through SH2 and SH3 domains","volume":"3","author":"Mayer","year":"1993","journal-title":"Trends Cell Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41417-021-00370-0","article-title":"Downregulation of TMEM220 promotes tumor progression in Hepatocellular Carcinoma","volume":"29","author":"Li","year":"2021","journal-title":"Cancer Gene Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3892\/etm.2013.1451","article-title":"Treadmill exercise reduces spinal cord injury-induced apoptosis by activating the PI3K\/Akt pathway in rats","volume":"7","author":"Jung","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"65281","DOI":"10.18632\/oncotarget.18370","article-title":"Methylomics of nitroxidative stress on precancerous cells reveals DNA methylation alteration at the transition from in situ to invasive cervical cancer","volume":"8","author":"Su","year":"2017","journal-title":"Oncotarget"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, H., Fan, C., Hildesj\u00f6, C., Shen, B., and Sun, X.F. (2022). Loss of CHGA protein as a potential biomarker for colon cancer diagnosis: A study on biomarker discovery by machine learning and confirmation by immunohistochemistry in colorectal cancer tissue microarrays. Cancers, 14.","DOI":"10.1101\/2022.04.04.22271362"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Kirouac, D.C., Du, J., Lahdenranta, J., Onsum, M.D., Nielsen, U.B., Schoeberl, B., and McDonagh, C.F. (2016). HER2+ cancer cell dependence on PI3K vs. MAPK signaling axes is determined by expression of EGFR.; ERBB3 and CDKN1B. PLoS Comput. Biol., 12.","DOI":"10.1371\/journal.pcbi.1004827"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ccr.2014.02.025","article-title":"ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics","volume":"25","author":"Arteaga","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1177\/1758834014530023","article-title":"The PI3K\/AKT\/mTOR pathway in breast cancer: Targets; trials and biomarkers","volume":"6","author":"Paplomata","year":"2014","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Li, H., Prever, L., Hirsch, E., and Gulluni, F. (2021). Targeting PI3K\/AKT\/mTOR signaling pathway in breast cancer. Cancers, 13.","DOI":"10.3390\/cancers13143517"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/abbs\/gmu114","article-title":"Hippo pathway in mammary gland development and breast cancer","volume":"47","author":"Shi","year":"2014","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s12967-019-1869-4","article-title":"Analysis of the role of the Hippo pathway in cancer","volume":"17","author":"Han","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"111","DOI":"10.7150\/ijbs.23230","article-title":"The role of TGF-\u03b2\/SMAD4 signaling in cancer","volume":"14","author":"Zhao","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"101416","DOI":"10.1016\/j.isci.2020.101416","article-title":"Modeling the control of TGF-\u03b2\/Smad nuclear accumulation by the Hippo pathway effectors; Taz\/Yap","volume":"23","author":"Labibi","year":"2020","journal-title":"iScience"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10911-011-9203-7","article-title":"Crosstalk of TGF-\u03b2 and estrogen receptor signaling in breast cancer","volume":"16","author":"Band","year":"2011","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Moses, H., and Barcellos-Hoff, M.H. (2010). TGF-\u03b2 biology in mammary development and breast cancer. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a003277"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Alexander, P.B., and Wang, X.F. (2016). TGF-\u03b2 family signaling in the control of cell proliferation and survival. Cold Spring Harb. Perspect. Biol., 9.","DOI":"10.1101\/cshperspect.a022145"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"9160905","DOI":"10.1155\/2020\/9160905","article-title":"The emerging role of microRNAs in breast cancer","volume":"2020","author":"Yang","year":"2020","journal-title":"J. Oncol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.7150\/jca.71401","article-title":"Role and mechanism of miR-211 in human cancer","volume":"13","author":"Ye","year":"2022","journal-title":"J. Cancer"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"628367","DOI":"10.3389\/fonc.2020.628367","article-title":"The Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers","volume":"10","author":"Ray","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"D\u0105browski, M.J., and Wojta\u015b, B. (2019). Global DNA methylation patterns in human gliomas and their interplay with other epigenetic modifications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143478"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e326","DOI":"10.1002\/mco2.326","article-title":"Three-dimensional genome structure and function","volume":"4","author":"Tsai","year":"2023","journal-title":"MedComm."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e76539","DOI":"10.7554\/eLife.76539","article-title":"Cohesin-dependence of neuronal gene expression relates to chromatin loop length","volume":"11","author":"Calderon","year":"2022","journal-title":"eLife"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"iyac098","DOI":"10.1093\/genetics\/iyac098","article-title":"Altering enhancer\u2013promoter linear distance impacts promoter competition in cis and in trans","volume":"222","author":"Bateman","year":"2022","journal-title":"Genetics"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41580-019-0132-4","article-title":"The role of 3D genome organization in development and cell differentiation","volume":"20","author":"Zheng","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Sehgal, P., and Chaturvedi, P. (2023). Chromatin and cancer: Implications of disrupted chromatin organization in tumorigenesis and its diversification. Cancers, 15.","DOI":"10.3390\/cancers15020466"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.gde.2019.04.007","article-title":"Chromatin topology in development and disease","volume":"55","author":"Bompadre","year":"2019","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"111712","DOI":"10.1016\/j.mrfmmm.2020.111712","article-title":"Chromatin rigidity provides mechanical and genome protection","volume":"821","author":"Stephens","year":"2020","journal-title":"Mutat. Res."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Fischer, T., Hayn, A., and Mierke, C.T. (2020). Effect of Nuclear Stiffness on Cell Mechanics and Migration of Human Breast Cancer Cells. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00393"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3233\/BLC-211609","article-title":"Role of chromatin modifying complexes and therapeutic opportunities in bladder cancer","volume":"8","author":"Meghani","year":"2022","journal-title":"Bladder Cancer"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.15252\/embr.201541852","article-title":"Dynamic cohesin-mediated chromatin architecture controls epithelial\u2013mesenchymal plasticity in cancer","volume":"17","author":"Yun","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Hao, Y., Baker, D., and ten Dijke, P. (2019). TGF-\u03b2-mediated epithelial-mesenchymal transition and cancer metastasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112767"},{"key":"ref_168","first-page":"110","article-title":"Monte Carlo feature selection for supervised classification","volume":"24","author":"Enroth","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gkj144","article-title":"The UCSC Genome Browser Database: Update 2006","volume":"34","author":"Hinrichs","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: A flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_172","unstructured":"Weisenberger, D.J., Van Den Berg, D., Pan, F., Berman, B.P., and Laird, P.W. (2024, September 21). Comprehensive DNA Methylation Analysis on the Illumina \u00ae Infinium \u00ae Assay Platform. Available online: https:\/\/www.illumina.com\/content\/dam\/illumina-marketing\/documents\/products\/appnotes\/appnote_dna_methylation_analysis_infinium.pdf."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1093\/bib\/bby128","article-title":"miR+Pathway: The integration and visualization of miRNA and KEGG pathways","volume":"21","author":"Pian","year":"2019","journal-title":"Brief. Bioinform."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: An online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Pongubala, J.M.R., and Murre, C. (2021). Spatial organization of chromatin: Transcriptional control of adaptive immune cell development. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.633825"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"D252","DOI":"10.1093\/nar\/gkx1106","article-title":"HOCOMOCO: Towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis","volume":"46","author":"Kulakovskiy","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_178","unstructured":"Stojnic, R., and Diez, D. (2024, August 09). PWMEnrich: PWM Enrichment Analysis. Bioconductor 2024. Available online: https:\/\/bioconductor.org\/packages\/release\/bioc\/html\/PWMEnrich.html."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","article-title":"FIMO: Scanning for occurrences of a given motif","volume":"27","author":"Grant","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"W253","DOI":"10.1093\/nar\/gkm272","article-title":"STAMP: A web tool for exploring DNA-binding motif similarities","volume":"35","author":"Mahony","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_181","first-page":"D489","article-title":"Pathway Commons 2019 Update: Integration; analysis and exploration of pathway data","volume":"48","author":"Rodchenkov","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1101\/gr.205062.116","article-title":"An integrated 3-Dimensional Genome Modeling Engine for data-driven simulation of spatial genome organization","volume":"26","author":"Tang","year":"2016","journal-title":"Genome Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6558\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:06:29Z","timestamp":1760033189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":182,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146558"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146558","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]}}}