{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARID4B is a multifunctional chromatin regulator that plays context‐dependent roles in normal development and in cancer. In hematopoietic cells and leukemogenesis, ARID4B—often in combination with its homolog ARID4A—modulates epigenetic programs, and its deficiency (or haploinsufficiency) is associated with aberrant histone methylation and disruption of critical transcriptional networks leading to defective blood cell production and accelerated progression to acute myeloid leukemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the reproductive system, ARID4B is highly expressed in Sertoli cells where it functions as a transcriptional coactivator for both the androgen receptor and the retinoblastoma protein. This activity supports the formation and maintenance of the blood–testis barrier, proper spermatogenic progression, and niche establishment for spermatogonial stem cells; its loss leads to severe spermatogenic arrest and male infertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, ARID4B exhibits dual and context‐specific functions. In breast cancer, increased ARID4B expression enhances primary tumor growth, cell migration, invasion, and metastasis, likely through interactions with chromatin‐modifying complexes and metastasis suppressors, with its high levels correlating with poor metastasis‐free survival in estrogen receptor–positive patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Conversely, in prostate cancer, ARID4B along with ARID4A appears to act as a tumor suppressor, as their downregulation—mediated in part by miR‑30d—is associated with higher Gleason scores and early biochemical recurrence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In hepatocellular carcinoma and certain brain tumors, ARID4B is upregulated and its high expression is linked to vascular invasion, advanced histologic grade, and poorer patient outcomes, underscoring its oncogenic potential in these contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, ARID4B is involved in early developmental decisions. It is required for the proper activation of meso/endodermal gene expression programs during the exit from pluripotency, a process mediated in part through its association with SIN3A and HDAC1 to maintain appropriate histone acetylation at key developmental loci."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In hematopoietic stem/progenitor cells, ARID4B modulates intracellular KITLG/KIT signaling to ensure proper differentiation, highlighting its broader importance in lineage commitment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Thus, ARID4B functions as a versatile regulator of gene expression through chromatin modulation, contributing to lineage differentiation, tissue homeostasis, and tumor progression—with its role varying by tissue type and tumor context. Its regulation by microRNAs (e.g., miR‑519b‑3p in rectal cancer and miR‑30d in prostate cancer) further underscores its potential as both a prognostic biomarker and therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mei-Yi Wu, Karen W Eldin, Arthur L Beaudet "}, {"type": "b", "children": [{"type": "t", "text": "Identification of chromatin remodeling genes Arid4a and Arid4b as leukemia suppressor genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/djn253"}], "href": "https://doi.org/10.1093/jnci/djn253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18728284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18728284"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ray-Chang Wu, Ming Jiang, Arthur L Beaudet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARID4A and ARID4B regulate male fertility, a functional link to the AR and RB pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1218318110"}], "href": "https://doi.org/10.1073/pnas.1218318110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23487765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23487765"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ray-Chang Wu, Yang Zeng, I-Wen Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2015-1089"}], "href": "https://doi.org/10.1210/me.2015-1089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26258622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26258622"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ray-Chang Wu, Yang Zeng, Yu-Fang Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Temporal-Spatial Establishment of Initial Niche for the Primary Spermatogonial Stem Cell Formation Is Determined by an ARID4B Regulatory Network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/stem.2597"}], "href": "https://doi.org/10.1002/stem.2597"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28207192"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28207192"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Scott F Winter, Luanne Lukes, Renard C Walker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Allelic variation and differential expression of the mSIN3A histone deacetylase complex gene Arid4b promote mammary tumor growth and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1002735"}], "href": "https://doi.org/10.1371/journal.pgen.1002735"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22693453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22693453"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jinfeng Zhang, Siyu Hou, Zilong You, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and prognostic values of ARID family members in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.202489"}], "href": "https://doi.org/10.18632/aging.202489"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33592583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33592583"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ying-Ke Liang, Zhao-Dong Han, Jian-Ming Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of ARID4A and ARID4B promote tumor progression and directly regulated by microRNA-30d in patient with prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.26913"}], "href": "https://doi.org/10.1002/jcb.26913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29797600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29797600"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rongchang Wang, Zheng Yu, Fan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of ARID4B predicts poor survival in patients with hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humpath.2017.12.012"}], "href": "https://doi.org/10.1016/j.humpath.2017.12.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29288040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29288040"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Wen-Chiuan Tsai, Dueng-Yuan Hueng, Shin Nieh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARID4B is a good biomarker to predict tumour behaviour and decide WHO grades in gliomas and meningiomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Pathol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jclinpath-2016-203804"}], "href": "https://doi.org/10.1136/jclinpath-2016-203804"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27451434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27451434"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Nihal Terzi Cizmecioglu, Jialiang Huang, Ezgi G Keskin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.015534"}], "href": "https://doi.org/10.1074/jbc.RA120.015534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33454011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33454011"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "In-Chi Young, Bogang Wu, Jaclyn Andricovich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differentiation of fetal hematopoietic stem cells requires ARID4B to restrict autocrine KITLG/KIT-Src signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.110036"}], "href": "https://doi.org/10.1016/j.celrep.2021.110036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34818550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34818550"}]}]}]}