{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZNF750 is a critical transcription factor that orchestrates epidermal cell differentiation and skin homeostasis. Its discovery in familial psoriasis—with a dominant mutation leading to clinical psoriasiform phenotypes—established its pivotal role in maintaining proper epidermal barrier function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Subsequent work demonstrated that ZNF750 is indispensable for terminal differentiation of keratinocytes, acting downstream of the master regulator p63 to induce key differentiation effectors such as KLF4, while directly repressing progenitor cell genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, the transcriptional network of ZNF750 extends to the regulation of genes like CALML5—which contributes to intercellular adhesion—and involves cooperation with chromatin regulators to suppress innate immune receptors, thereby preventing overzealous inflammation in the skin."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in normal epidermal differentiation, ZNF750 functions as a potent tumor suppressor across a variety of epithelial cancers. Genetic studies have revealed frequent mutations and diminished nuclear expression of ZNF750 in malignancies such as esophageal squamous cell carcinoma, nasopharyngeal carcinoma, and oral, colonic, melanocytic, and sebaceous carcinomas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": " In nasopharyngeal carcinoma, for instance, epitranscriptomic modifications (m6A) lower ZNF750 expression, and re‐expression triggers a tumor repressor cascade via the FGF14 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Similar tumor‐suppressive roles have been uncovered in sebaceous carcinoma and oral squamous cell carcinoma, where ZNF750 loss correlates with enhanced cell proliferation, migration, and epithelial–mesenchymal transition—partly through derepression of factors such as SNAI1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": " Its significance extends to colonic cancer, melanoma, and even metastatic prostate cancer, where reduced nuclear positivity correlates with poorer patient outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies underscore the dual role of ZNF750 as both a master regulator of epidermal differentiation and a broad-spectrum tumor suppressor. Its regulatory functions are mediated through complex interactions with transcription factors, epigenetic modifiers, and non‐coding RNAs—which together coordinate the balance between maintaining differentiated states and preventing malignant transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": " Such multifaceted roles not only enhance our understanding of epithelial biology in health and disease but also highlight ZNF750 as a promising prognostic biomarker and potential therapeutic target.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chi-Fan Yang, Wuh-Liang Hwu, Li-Cheng Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A promoter sequence variant of ZNF750 is linked with familial psoriasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2008.1"}], "href": "https://doi.org/10.1038/jid.2008.1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18256691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18256691"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ramon Y Birnbaum, Genki Hayashi, Idan Cohen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association analysis identifies ZNF750 regulatory variants in psoriasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2350-12-167"}], "href": "https://doi.org/10.1186/1471-2350-12-167"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22185198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22185198"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "George L Sen, Lisa D Boxer, Dan E Webster, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2011.12.001"}], "href": "https://doi.org/10.1016/j.devcel.2011.12.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22364861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22364861"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Idan Cohen, Ramon Y Birnbaum, Keren Leibson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750 is expressed in differentiated keratinocytes and regulates epidermal late differentiation genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0042628"}], "href": "https://doi.org/10.1371/journal.pone.0042628"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22936986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22936986"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sohei Kitazawa, Yuki Takaoka, Yasuo Ueda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of calmodulin-like protein 5 as tumor-suppressor gene silenced during early stage of carcinogenesis in squamous cell carcinoma of uterine cervix."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.33687"}], "href": "https://doi.org/10.1002/ijc.33687"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33997976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33997976"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lu Xia, Hexin Lin, Yanming Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750 facilitates carcinogenesis via promoting the expression of long non-coding RNA "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "CYTOR"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and influences pharmacotherapy response in colon adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Zhejiang Univ Sci B (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1631/jzus.B2100939"}], "href": "https://doi.org/10.1631/jzus.B2100939"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35794688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35794688"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ye Liu, Yifang Chen, Uyanga Batzorig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transcription regulators ZNF750 and LSD1/KDM1A dampen inflammation on the skin's surface by silencing pattern recognition receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2024.09.002"}], "href": "https://doi.org/10.1016/j.immuni.2024.09.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39353440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39353440"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "T Dębniak, E Soczawa, M Boer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants of ZNF750, RPTOR and TRAF3IP2 genes and psoriasis risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Dermatol Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00403-013-1407-9"}], "href": "https://doi.org/10.1007/s00403-013-1407-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24005976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24005976"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Lisa D Boxer, Brook Barajas, Shiying Tao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.246579.114"}], "href": "https://doi.org/10.1101/gad.246579.114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25228645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25228645"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jia-Jie Hao, De-Chen Lin, Huy Q Dinh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3683"}], "href": "https://doi.org/10.1038/ng.3683"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27749841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27749841"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ryota Otsuka, Yasunori Akutsu, Haruhito Sakata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750 Expression as a Novel Candidate Biomarker of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncology (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000476068"}], "href": "https://doi.org/10.1159/000476068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28558382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28558382"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ryota Otsuka, Yasunori Akutsu, Haruhito Sakata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750 Expression Is a Potential Prognostic Biomarker in Esophageal Squamous Cell Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncology (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000484932"}], "href": "https://doi.org/10.1159/000484932"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29216641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29216641"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Li Pan, Hongli Yang, Cong Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750 inhibited the malignant progression of oral squamous cell carcinoma by regulating tumor vascular microenvironment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2018.06.001"}], "href": "https://doi.org/10.1016/j.biopha.2018.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29890464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29890464"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Panpan Zhang, Qiuping He, Yuan Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "m"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "6"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-1224-3"}], "href": "https://doi.org/10.1038/s41419-018-1224-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30518868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30518868"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jeffrey P North, David A Solomon, Justin Golovato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of ZNF750 in ocular and cutaneous sebaceous carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cutan Pathol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cup.13516"}], "href": "https://doi.org/10.1111/cup.13516"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31148199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31148199"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Xianbin Liu, Yikun Yang, Cong Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNA sequencing analysis of the CAL-27 cell response to over-expressed ZNF750 gene revealed an extensive regulation on cell cycle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2019.109377"}], "href": "https://doi.org/10.1016/j.biopha.2019.109377"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31545271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31545271"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Pengzhou Kong, Enwei Xu, Yanghui Bi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel ESCC-related gene ZNF750 as potential Prognostic biomarker and inhibits Epithelial-Mesenchymal Transition through directly depressing SNAI1 promoter in ESCC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theranostics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/thno.38210"}], "href": "https://doi.org/10.7150/thno.38210"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32042337"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32042337"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jie Qu, Xiuqin Zhang, Xiying Lv "}, {"type": "b", "children": [{"type": "t", "text": "Zinc finger protein 750(ZNF750), negatively regulated by miR-17-5p, inhibits proliferation, motility and invasion of colonic cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gene Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jgm.3195"}], "href": "https://doi.org/10.1002/jgm.3195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32246873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32246873"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yong Du, Guozhong Lv, Changrui Jing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750 inhibits the proliferation and invasion of melanoma cells through modulating the Wnt/b-catenin signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Folia Histochem Cytobiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5603/FHC.a2020.0026"}], "href": "https://doi.org/10.5603/FHC.a2020.0026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33185885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33185885"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Yue Xiao, Yanjun Duan, Yongjie Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resveratrol suppresses malignant progression of oral squamous cell carcinoma cells by inducing the ZNF750/RAC1 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1940616"}], "href": "https://doi.org/10.1080/21655979.2021.1940616"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34176441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34176441"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Ruhui Wen, Chao Chen, Xiaohua Zhong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAX6 upstream antisense RNA (PAUPAR) inhibits colorectal cancer progression through modulation of the microRNA (miR)-17-5p / zinc finger protein 750 (ZNF750) axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1940071"}], "href": "https://doi.org/10.1080/21655979.2021.1940071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34288812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34288812"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Masahiko Takahashi, Kazuyoshi Hosomichi, Hirofumi Nakaoka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biased expression of mutant alleles in cancer-related genes in esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Esophagus (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10388-021-00900-7"}], "href": "https://doi.org/10.1007/s10388-021-00900-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35013873"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35013873"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Manuela Montanaro, Massimiliano Agostini, Lucia Anemona, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF750: A Novel Prognostic Biomarker in Metastatic Prostate Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms24076519"}], "href": "https://doi.org/10.3390/ijms24076519"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37047491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37047491"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Xue-Ting Hu, Xiao-Feng Wu, Lu-Min Sui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GRHL3-regulated long non-coding RNA lnc-DC modulates keratinocytes differentiation by interacting with IGF2BP2 and up-regulating ZNF750."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jdermsci.2024.02.003"}], "href": "https://doi.org/10.1016/j.jdermsci.2024.02.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38383230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38383230"}]}]}]}