{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:01:16Z","timestamp":1781154076917,"version":"3.54.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chromatin regulators (CRs) have been reported to modulate tumorigenesis and progression in multiple pathophysiological processes, but little is known about theirs role and association with the immune microenvironment in breast cancer (BRCA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study identified differential CRs gene expression in BRCA using transcriptome sequencing data and single-cell RNA sequencing data. We investigated the biological function of HMGB3 gene using western blot, transwell assay and immunohistochemistry (IHC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this research, eleven CRs were discovered and utilized to create a prognostic model. Using median risk scores, patients were sorted into high- and low-risk groups. The nomogram created from this model precisely predicted overall survival (OS). Low-risk patients had notably higher immune cells infiltrating. IHC provided additional evidence that the expression levels of HMGB3 are closely linked to BRCA.\n                      <jats:italic>In vitro<\/jats:italic>\n                      functional assays demonstrated that HMGB3 enhances the invasion of BRCA cells and facilitates malignant progression by controlling cell cycle.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Based on bioinformatics analysis of the prognostic value of CRs in BRCA, we identified that HMGB3 as a novel target molecule to promote the occurrence and development of BRCA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1835558","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:38:09Z","timestamp":1781152689000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bulk and single-cell RNA sequencing data identified HMGB3 of chromatin regulators as a breast cancer biomarker associated with the cell cycle"],"prefix":"10.3389","volume":"16","author":[{"given":"Huan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mudanjiang Medical University","place":["Mudanjiang, Heilongjiang, China"]},{"name":"Department of Pathology and Transfusion Medicine, The 961st Hospital of the Joint Logistics, Support Force of The Chinese People\u2019s Liberation Army","place":["Qiqihar, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mudanjiang Medical University","place":["Mudanjiang, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingyuan","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Transfusion Medicine, The 961st Hospital of the Joint Logistics, Support Force of The Chinese People\u2019s Liberation Army","place":["Qiqihar, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Laboratory, Daqing Traditional Chinese Medicine Hospital","place":["Daqing, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheyao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Laboratory, Bei\u2019an First People\u2019s Hospital","place":["Heihe, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjiao","family":"An","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mudanjiang Medical University","place":["Mudanjiang, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mudanjiang Medical University","place":["Mudanjiang, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ji","sequence":"additional","affiliation":[{"name":"Unit 93313, People\u2019s Liberation Army of China","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Transfusion Medicine, The 961st Hospital of the Joint Logistics, Support Force of The Chinese People\u2019s Liberation Army","place":["Qiqihar, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjun","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mudanjiang Medical University","place":["Mudanjiang, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1158\/1055-9965.epi-15-0578","article-title":"Global cancer incidence and mortality rates and trends--an update","volume":"25","author":"Torre","year":"2016","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03502-3","article-title":"Global patterns and trends in breast cancer incidence and mortality across 185 countries","volume":"31","author":"Kim","year":"2025","journal-title":"Nat Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.01.007","article-title":"Distinct cellular mechanisms underlie chemotherapies and PD-L1 blockade combinations in triple-negative breast cancer","volume":"43","author":"Zhang","year":"2025","journal-title":"Cancer Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s43018-024-00890-2","article-title":"Neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in women with early HER2-positive breast cancer: the randomized phase 2 ABCSG-52\/ATHENE trial","volume":"6","author":"Rinnerthaler","year":"2025","journal-title":"Nat Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky679","article-title":"FACER: comprehensive molecular and functional characterization of epigenetic chromatin regulators","volume":"46","author":"Lu","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3554","article-title":"Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer","volume":"14","author":"Plass","year":"2013","journal-title":"Nat Rev Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/nrm.2017.94","article-title":"Emerging roles of linker histones in regulating chromatin structure and function","volume":"19","author":"Fyodorov","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature24050","article-title":"Cytoplasmic chromatin triggers inflammation in senescence and cancer","volume":"550","author":"Dou","year":"2017","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1146\/annurev-immunol-031210-101303","article-title":"Chromatin contributions to the regulation of innate immunity","volume":"32","author":"Smale","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00589","article-title":"Downregulation of HMGA1 mediates autophagy and inhibits migration and invasion in bladder cancer via miRNA-221\/TP53INP1\/p-ERK axis","volume":"10","author":"Liu","year":"2020","journal-title":"Front Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.06.025","article-title":"DNMT1-mediated methylation of BEX1 regulates stemness and tumorigenicity in liver cancer","volume":"75","author":"Wang","year":"2021","journal-title":"J Hepatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107753","article-title":"Tumor microenvironment as a therapeutic target in cancer","volume":"221","author":"Xiao","year":"2021","journal-title":"Pharmacol Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-18-3962","article-title":"The tumor microenvironment innately modulates cancer progression","volume":"79","author":"Hinshaw","year":"2019","journal-title":"Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3649","article-title":"Integration of comprehensive genomic profiling, tumor mutational burden, and PD-L1 expression to identify novel biomarkers of immunotherapy in non-small cell lung cancer","volume":"10","author":"Shi","year":"2021","journal-title":"Cancer Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102434","article-title":"Development and validation of a metastasis-associated prognostic signature based on single-cell RNA-seq in clear cell renal cell carcinoma","volume":"11","author":"Zhang","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1101\/gr.191098.115","article-title":"The first five years of single-cell cancer genomics and beyond","volume":"25","author":"Navin","year":"2015","journal-title":"Genome Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20211033","article-title":"Understanding breast cancer as a global health concern","volume":"95","author":"Wilkinson","year":"2022","journal-title":"Br J Radiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0646","article-title":"MOZ and Menin-MLL complexes are complementary regulators of chromatin association and transcriptional output in gastrointestinal stromal tumor","volume":"12","author":"Hemming","year":"2022","journal-title":"Cancer Discov"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2022-0266","article-title":"A novel chromatin regulator signature predicts the prognosis, clinical features and immunotherapy of colon cancer","volume":"14","author":"Li","year":"2022","journal-title":"Epigenomics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.06.002","article-title":"ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma","volume":"489","author":"Miyashita","year":"2020","journal-title":"Cancer Lett"},{"key":"B22","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/s13046-023-02806-x","article-title":"ERCC6L facilitates the onset of mammary neoplasia and promotes the high Malignance of breast cancer by accelerating the cell cycle","volume":"42","author":"Yang","year":"2023","journal-title":"J Exp Clin Cancer Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1007\/s12032-022-01812-x","article-title":"IKZF3 amplification frequently occurs in HER2-positive breast cancer and is a potential therapeutic target","volume":"39","author":"Lin","year":"2022","journal-title":"Med Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-023-04777-1","article-title":"KDM4B down-regulation facilitated breast cancer cell stemness via PHGDH upregulation in H3K36me3-dependent manner","volume":"479","author":"Wang","year":"2024","journal-title":"Mol Cell Biochem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15844","article-title":"The duality of PRDM proteins: epigenetic and structural perspectives","volume":"289","author":"Di Tullio","year":"2022","journal-title":"FEBS J"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/2736932","article-title":"Chromatin regulator-related gene signature for predicting prognosis and immunotherapy efficacy in breast cancer","volume":"2023","author":"Feng","year":"2023","journal-title":"J Oncol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1247\/csf.13010","article-title":"Prdm12 is induced by retinoic acid and exhibits anti-proliferative properties through the cell cycle modulation of P19 embryonic carcinoma cells","volume":"38","author":"Yang.","year":"2013","journal-title":"Cell Struct Funct"},{"key":"B28","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41523-022-00484-0","article-title":"LINC00589-dominated ceRNA networks regulate multiple chemoresistance and cancer stem cell-like properties in HER2(+) breast cancer","volume":"8","author":"Bai","year":"2022","journal-title":"NPJ Breast Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81918-2","article-title":"SWI2\/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions","volume":"88","author":"Pazin","year":"1997","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109341","article-title":"RAD54B potentiates tumor growth and predicts poor prognosis of patients with luminal A breast cancer","volume":"118","author":"Zhang","year":"2019","journal-title":"BioMed Pharmacother"},{"key":"B31","article-title":"High expression of Sirt7 served as a predictor of adverse outcome in breast cancer","volume":"8","author":"Geng","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.75340","article-title":"SIRT7 downregulation promotes breast cancer metastasis via LAP2alpha-induced chromosomal instability","volume":"19","author":"Huo","year":"2023","journal-title":"Int J Biol Sci"},{"key":"B33","article-title":"The estrogen-regulated protein, TFF1, stimulates migration of human breast cancer cells","volume":"16","author":"Prest","year":"2002"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2156","article-title":"TFF1 activates p53 through down-regulation of miR-504 in gastric cancer","volume":"5","author":"Soutto","year":"2014","journal-title":"Oncotarget"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.812786","article-title":"Construction of a prognostic model for hypoxia-related lncRNAs and prediction of the immune landscape in the digestive system pan-cancer","volume":"12","author":"He","year":"2022","journal-title":"Front Oncol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.canlet.2019.07.017","article-title":"Adoptive CD8+ T cell therapy against cancer: challenges and opportunities","volume":"462","author":"Jiang","year":"2019","journal-title":"Cancer Lett"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.7150\/thno.17092","article-title":"Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous leukemia cell growth","volume":"7","author":"Bellavia","year":"2017","journal-title":"Theranostics"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.101041","article-title":"The promising role of tumor-associated macrophages in the treatment of cancer","volume":"73","author":"Wang","year":"2024","journal-title":"Drug Resist Update"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121137","article-title":"M1 macrophage exosomes engineered to foster M1 polarization and target the IL-4 receptor inhibit tumor growth by reprogramming tumor-associated macrophages into M1-like macrophages","volume":"278","author":"Gunassekaran","year":"2021","journal-title":"Biomaterials"},{"key":"B40","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.coi.2018.03.009","article-title":"Plasticity of myeloid-derived suppressor cells in cancer","volume":"51","author":"Tcyganov","year":"2018","journal-title":"Curr Opin Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1503093","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N Engl J Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01786-6","article-title":"Progranulin induces immune escape in breast cancer via up-regulating PD-L1 expression on tumor-associated macrophages (TAMs) and promoting CD8(+) T cell exclusion","volume":"40","author":"Fang","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003087","article-title":"Tumor mutation burden for predicting immune checkpoint blockade response: the more, the better","volume":"10","author":"Zheng","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5214","article-title":"Hmg4, a new member of the Hmg1\/2 gene family","volume":"49","author":"Vaccari.","year":"1998","journal-title":"Genomics"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2020.31.e91","article-title":"High mobility group box 3 promotes cervical cancer proliferation by regulating Wnt\/beta-catenin pathway","volume":"31","author":"Zhuang","year":"2020","journal-title":"J Gynecol Oncol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.891482","article-title":"HMGB3 is a potential therapeutic target by affecting the migration and proliferation of colorectal cancer","volume":"10","author":"Gong","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s12890-021-01552-0","article-title":"Down-regulation of SNHG16 alleviates the acute lung injury in sepsis rats through miR-128-3p\/HMGB3 axis","volume":"21","author":"Sun","year":"2021","journal-title":"BMC Pulm Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00655","article-title":"Exploring the metabolic vulnerabilities of epithelial-mesenchymal transition in breast cancer","volume":"8","author":"Sun","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1186\/s13046-019-1415-5","article-title":"CyclinD1 inhibits dicer and crucial miRNA expression by chromatin modification to promote the progression of intrahepatic cholangiocarcinoma","volume":"38","author":"Qi","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031211","article-title":"p27, the cell cycle and Alzheimer s disease","volume":"23","author":"Garcia-Osta","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B51","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/mc.23861","article-title":"HMGB3 contributes to anti-PD-1 resistance by inhibiting IFN-gamma-driven ferroptosis in TNBC","volume":"64","author":"Luo","year":"2025","journal-title":"Mol Carcinog"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.s204357","article-title":"HMGB3 silence inhibits breast cancer cell proliferation and tumor growth by interacting with hypoxia-inducible factor 1alpha","volume":"11","author":"Gu","year":"2019","journal-title":"Cancer Manag Res"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1835558\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:38:12Z","timestamp":1781152692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1835558\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":52,"alternative-id":["10.3389\/fonc.2026.1835558"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1835558","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]},"article-number":"1835558"}}