{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZNF300 is a member of the KRAB/C2H2 zinc finger transcription factor family that plays diverse roles in gene regulation. Epigenetic alterations affecting a related long intergenic non‐coding RNA, ZNF300P1, have been implicated in ovarian cancer by perturbing cell cycle control and cell motility, thereby potentially promoting metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, ZNF300 functions as a sequence‐specific DNA binding protein. It recognizes motifs such as C(t/a)GGGGG(c/g)G and directly regulates target gene promoters – for example, it activates the IL-2Rβ promoter through direct binding, in cooperation with factors like Egr1. In addition, ZNF300 modulates pro-tumorigenic signaling by enhancing NF‑κB activation via interactions with TRAF2 and IKKβ, as well as by increasing ERK1/2 phosphorylation and the expression of oncogenic mediators (c-myc, IL-6, IL-8) while repressing cell cycle inhibitors. Recent work also demonstrates its role in metabolic regulation, where ZNF300 binds to the PPARα promoter to promote fatty acid oxidation; intriguingly, its expression in hepatocytes can be silenced by DNMT3a-mediated methylation. A novel splice variant, ZNF300-B, further suggests tissue-specific functional nuances."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the oncogenic potential of ZNF300 is underscored by its ability to stimulate cancer cell proliferation and metastasis, effectively linking inflammatory signaling pathways with tumorigenesis. Although distinct studies have also explored chemoresistance in lung cancer and challenges in hepatocellular carcinoma treatment – contexts that add to the complexity of malignancy – these investigations emphasize the broader biological and clinical relevance of transcriptional regulators like ZNF300."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brian Gloss, Kim Moran-Jones, Vita Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF300P1 encodes a lincRNA that regulates cell polarity and is epigenetically silenced in type II epithelial ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-13-3"}], "href": "https://doi.org/10.1186/1476-4598-13-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24393131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24393131"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tao Wang, Xian-guo Wang, Jun-hua Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of the human ZNF300 gene enhances growth and metastasis of cancer cells through activating NF-kB pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1582-4934.2011.01388.x"}], "href": "https://doi.org/10.1111/j.1582-4934.2011.01388.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21777376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21777376"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jun-Hua Xu, Tao Wang, Xian-Guo Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PU.1 can regulate the ZNF300 promoter in APL-derived promyelocytes HL-60."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.leukres.2010.04.009"}], "href": "https://doi.org/10.1016/j.leukres.2010.04.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20471086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20471086"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hongling Qiu, Lu Xue, Li Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the DNA binding element of the human ZNF300 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2478/s11658-008-0005-x"}], "href": "https://doi.org/10.2478/s11658-008-0005-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18350257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18350257"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Feng-Juan Yan, Yong-Jian Wang, Shi-Ran Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF300 stimulates fatty acid oxidation and alleviates hepatosteatosis through regulating PPARα."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20180517"}], "href": "https://doi.org/10.1042/BCJ20180517"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30568000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30568000"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lu Xue, Hongling Qiu, Jian Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZNF300, a recently identified human transcription factor, activates the human IL-2Rβ promoter through the overlapping ZNF300/EGR1 binding site."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2478/s11658-010-0025-1"}], "href": "https://doi.org/10.2478/s11658-010-0025-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20585888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20585888"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yi Cao, Ji-Xi Li, Chao-Neng Ji, et al. 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