{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPHF8 is a Jumonji C‐domain–containing histone demethylase that plays a central role in epigenetic regulation by removing repressive methyl marks from histone substrates such as H3K9me1/2, H3K27me2, and H4K20me1. Its PHD finger domain enables binding to H3K4me2/3 at gene promoters, thereby facilitating transcriptional activation. Through these activities, PHF8 helps regulate key developmental and cell fate genes and is critically involved in neuronal differentiation; mutations in PHF8 have been linked to X‐linked mental retardation and craniofacial abnormalities (e.g., cleft lip/palate). These studies demonstrate that defective demethylase activity—whether by point mutations (e.g. F279S) or protein misregulation—leads to imbalances in histone methylation and consequent aberrant gene expression underlying neurodevelopmental defects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental role in chromatin regulation, PHF8 is intricately involved in cell cycle progression and maintenance of genome stability. It regulates the expression of key cell cycle genes—such as those modulated by E2F transcription factors—and modulates rDNA transcription by acting at nucleolar promoters. In mitosis, PHF8 itself is tightly regulated through phosphorylation and ubiquitin‐dependent degradation (for example, via interaction with APC^CDC20), whereas its stabilization can be promoted by deubiquitinases like USP7. Moreover, PHF8 interacts with nuclear receptors (e.g. RARα) and other transcription factors (such as ZNF711 and c‐Myc) to integrate epigenetic signals with DNA replication and repair processes, thereby further linking its activity to both normal cell function and stress responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPHF8’s aberrant regulation has been associated with oncogenesis and metastasis in a broad spectrum of cancers, including breast, esophageal, colorectal, lung, prostate, and hepatocellular carcinoma, as well as in certain leukemias. In these contexts, overexpression or enhanced activity of PHF8 promotes cell proliferation, migration, invasion, and epithelial–mesenchymal transition through the activation of oncogenic signaling pathways such as Wnt/β‐catenin and MEK/ERK. Moreover, PHF8 is subject to regulation by microRNAs and forms part of regulatory axes with transcription factors like MYC, further underscoring its potential as both a prognostic biomarker and a therapeutic target. In some studies, pharmacological inhibition of enzymes or signaling components downstream of PHF8 has demonstrated promising antitumor effects, highlighting the translational relevance of targeting PHF8‐mediated epigenetic reprogramming."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "44"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jeffrey B Cheng, Daniel L Motola, David J Mangelsdorf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307028200"}], "href": "https://doi.org/10.1074/jbc.M307028200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12867411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12867411"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "F Laumonnier, S Holbert, N Ronce, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2004.029439"}], "href": "https://doi.org/10.1136/jmg.2004.029439"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16199551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16199551"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "A M Koivisto, S Ala-Mello, S Lemmelä, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1399-0004.2007.00836.x"}], "href": "https://doi.org/10.1111/j.1399-0004.2007.00836.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17661819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17661819"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Christoph Loenarz, Wei Ge, Mathew L Coleman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp480"}], "href": "https://doi.org/10.1093/hmg/ddp480"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19843542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19843542"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wyatt W Yue, Viktorija Hozjan, Wei Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2009.12.055"}], "href": "https://doi.org/10.1016/j.febslet.2009.12.055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20067792"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20067792"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lin Yu, Yang Wang, Shuo Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into a novel histone demethylase PHF8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2010.8"}], "href": "https://doi.org/10.1038/cr.2010.8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20101266"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20101266"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Weijun Feng, Masato Yonezawa, Jing Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1778"}], "href": "https://doi.org/10.1038/nsmb.1778"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20208542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20208542"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Daniela Kleine-Kohlbrecher, Jesper Christensen, Julien Vandamme, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.03.002"}], "href": "https://doi.org/10.1016/j.molcel.2010.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20346720"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20346720"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Klaus Fortschegger, Petra de Graaf, Nikolay S Outchkourov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHF8 targets histone methylation and RNA polymerase II to activate transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01520-09"}], "href": "https://doi.org/10.1128/MCB.01520-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20421419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20421419"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ziqi Zhu, Yanru Wang, Xia Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2010.75"}], "href": "https://doi.org/10.1038/cr.2010.75"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20531378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20531378"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jihui Qiu, Guang Shi, Yuanhui Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2010.81"}], "href": "https://doi.org/10.1038/cr.2010.81"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20548336"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20548336"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Hank H Qi, Madathia Sarkissian, Gang-Qing Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09261"}], "href": "https://doi.org/10.1038/nature09261"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20622853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20622853"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Wen Liu, Bogdan Tanasa, Oksana V Tyurina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09272"}], "href": "https://doi.org/10.1038/nature09272"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20622854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20622854"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "M Björkman, P Östling, V Härmä, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic knockdown of epigenetic enzymes identifies a novel histone demethylase PHF8 overexpressed in prostate cancer with an impact on cell proliferation, migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.512"}], "href": "https://doi.org/10.1038/onc.2011.512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22120715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22120715"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Yanping Wang, Steven J Marling, Jinge G Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Development of experimental autoimmune encephalomyelitis (EAE) in mice requires vitamin D and the vitamin D receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1206054109"}], "href": "https://doi.org/10.1073/pnas.1206054109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22592802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22592802"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Maria Francisca Arteaga, Jan-Henrik Mikesch, Jihui Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2013.02.014"}], "href": "https://doi.org/10.1016/j.ccr.2013.02.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23518351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23518351"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Jinge G Zhu, Justin T Ochalek, Martin Kaufmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo."}]}, {"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.1315006110"}], "href": "https://doi.org/10.1073/pnas.1315006110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24019477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24019477"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Xiujing Sun, Jihui Julia Qiu, Shengtao Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic features of PHF8 histone demethylase in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0077353"}], "href": "https://doi.org/10.1371/journal.pone.0077353"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24146981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24146981"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yuzhou Shen, Xufeng Pan, Heng Zhao "}, {"type": "b", "children": [{"type": "t", "text": "The histone demethylase PHF8 is an oncogenic protein in human non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.07.076"}], "href": "https://doi.org/10.1016/j.bbrc.2014.07.076"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25065740"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25065740"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Guang Shi, Meng Wu, Lan Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHD finger protein 2 (PHF2) represses ribosomal RNA gene transcription by antagonizing PHF finger protein 8 (PHF8) and recruiting methyltransferase SUV39H1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.571653"}], "href": "https://doi.org/10.1074/jbc.M114.571653"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25204660"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25204660"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Qian Wang, Shuai Ma, Nan Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI85747"}], "href": "https://doi.org/10.1172/JCI85747"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27183383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27183383"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Peterson Kariuki Maina, Peng Shao, Qi Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "c-MYC drives histone demethylase PHF8 during neuroendocrine differentiation and in castration-resistant prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.12310"}], "href": "https://doi.org/10.18632/oncotarget.12310"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27689328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27689328"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Akiyo Hirose, Wataru Ochiai, Yuka Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of CYP2R1 and CYP26A1 Expression Patterns in Regeneration in Mice with Liver Injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Pharm Bull (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1248/bpb.b16-00402"}], "href": "https://doi.org/10.1248/bpb.b16-00402"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27904037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27904037"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Wataru Ochiai, Akiyo Hirose, Taisuke Kawamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of the Drug-Metabolizing Enzyme CYP during Mouse Liver Development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Pharm Bull (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1248/bpb.b16-00479"}], "href": "https://doi.org/10.1248/bpb.b16-00479"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27904043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27904043"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Peterson Kariuki Maina, Peng Shao, Xiongfei Jia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylase PHF8 regulates hypoxia signaling through HIF1α and H3K4me3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Gene Regul Mech (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2017.07.005"}], "href": "https://doi.org/10.1016/j.bbagrm.2017.07.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28734980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28734980"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yao Lv, Yan Shi, Quanli Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylase PHF8 accelerates the progression of colorectal cancer and can be regulated by miR-488 in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2017.7130"}], "href": "https://doi.org/10.3892/mmr.2017.7130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28765946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28765946"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Livia Ulicna, Alzbeta Kalendova, Ilona Kalasova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PIP2 epigenetically represses rRNA genes transcription interacting with PHF8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Biol Lipids (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2017.12.008"}], "href": "https://doi.org/10.1016/j.bbalip.2017.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29246768"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29246768"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Yue Fu, Yaling Yang, Xiaoming Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone demethylase PHF8 promotes adult acute lymphoblastic leukemia through interaction with the MEK/ERK signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.01.049"}], "href": "https://doi.org/10.1016/j.bbrc.2018.01.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29330049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29330049"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Wuhua Zhou, Li Gong, Qinchuan Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHF8 upregulation contributes to autophagic degradation of E-cadherin, epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-018-0890-4"}], "href": "https://doi.org/10.1186/s13046-018-0890-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30180906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30180906"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Matthias S Leisegang, Lunda Gu, Jens Preussner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA-G."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.13337"}], "href": "https://doi.org/10.1002/1873-3468.13337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30758047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30758047"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Hong Ye, Qing Yang, Shujie Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHF8 Plays an Oncogene Function in Hepatocellular Carcinoma Formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504018X15410353669149"}], "href": "https://doi.org/10.3727/096504018X15410353669149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30764899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30764899"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Qi Liu, Nicholas C Borcherding, Peng Shao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contribution of synergism between PHF8 and HER2 signalling to breast cancer development and drug resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2019.102612"}], "href": "https://doi.org/10.1016/j.ebiom.2019.102612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31923801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31923801"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Yan Cheng, Na Liu, CaiFeng Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-383 inhibits proliferation, migration, and invasion in hepatocellular carcinoma cells by targeting PHF8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.1272"}], "href": "https://doi.org/10.1002/mgg3.1272"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32441881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32441881"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Lin-Lu Tseng, Hsin-Hung Cheng, Ta-Sen Yeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting the histone demethylase PHF8-mediated PKCα-Src-PTEN axis in HER2-negative gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1919766117"}], "href": "https://doi.org/10.1073/pnas.1919766117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32958674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32958674"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Qiuli Liu, Jian Pang, Lin-Ang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.5557"}], "href": "https://doi.org/10.1002/path.5557"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33009820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33009820"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Ming-Zhi Cai, Shao-Yan Wen, Xue-Jun Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MYC Regulates PHF8, Which Promotes the Progression of Gastric Cancer by Suppressing miR-22-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Technol Cancer Res Treat (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1533033820967472"}], "href": "https://doi.org/10.1177/1533033820967472"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33111613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33111613"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Yan Hu, Hanshuo Mu, Ying Yang "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylase PHF8 promotes cell growth and metastasis of non-small-cell lung cancer through activating Wnt/β-catenin signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histol Histopathol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14670/HH-18-349"}], "href": "https://doi.org/10.14670/HH-18-349"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34100557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34100557"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Loredana Poeta, Agnese Padula, Maria Brigida Lioi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of a Set of KDM5C Regulatory Genes Mutated in Neurodevelopmental Disorders Identifies Temporal Coexpression Brain Signatures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes12071088"}], "href": "https://doi.org/10.3390/genes12071088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34356104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34356104"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Shuai Ma, Jieyou Zhang, Qiushi Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disrupting PHF8-TOPBP1 connection elicits a breast tumor-specific vulnerability to chemotherapeutics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2022.01.010"}], "href": "https://doi.org/10.1016/j.canlet.2022.01.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35051531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35051531"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Rana S Moubarak, Ana de Pablos-Aragoneses, Vanessa Ortiz-Barahona, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.abi7127"}], "href": "https://doi.org/10.1126/sciadv.abi7127"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35179962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35179962"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Rui Feng, Zhongxing Li, Guangcheng Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NEDD4L represses prostate cancer cell proliferation via modulating PHF8 through the ubiquitin-proteasome pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Transl Oncol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12094-022-02933-5"}], "href": "https://doi.org/10.1007/s12094-022-02933-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36136271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36136271"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Yanan Liu, Longmiao Hu, Zhengzhen Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of PHF8 induces a viral mimicry response by activating endogenous retrotransposons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-023-39943-y"}], "href": "https://doi.org/10.1038/s41467-023-39943-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37454216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37454216"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Song Peng, Ze Wang, Peng Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.adf3566"}], "href": "https://doi.org/10.1126/sciadv.adf3566"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37531433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37531433"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Łukasz Witucki, Hieronim Jakubowski "}, {"type": "b", "children": [{"type": "t", "text": "Homocysteine metabolites impair the PHF8/H4K20me1/mTOR/autophagy pathway by upregulating the expression of histone demethylase PHF8-targeting microRNAs in human vascular endothelial cells and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.202302116R"}], "href": "https://doi.org/10.1096/fj.202302116R"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39323294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39323294"}]}]}]}