{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nJMJD8 is a member of the Jumonji C domain‐only protein family that, unlike many of its relatives acting in the nucleus, localizes to the lumen of the endoplasmic reticulum. In this unique subcellular niche, JMJD8 forms dimers or oligomers and interacts with proteins that mediate complex assembly and folding, suggesting a role in maintaining protein homeostasis and possibly influencing vascular and inflammatory functions during endothelial differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn tumor cells, modulation of JMJD8 expression has significant effects on proliferation and the DNA damage response. Knockdown of JMJD8 has been shown to increase cell proliferation while attenuating ionizing irradiation or chemotherapy‐induced DNA double‐strand breaks by upregulating key repair proteins, Ku70 and Ku80, via enhanced cyclooxygenase-2 (COX-2) expression. Moreover, JMJD8 influences the activation state of the AKT pathway by regulating AKT methylation—a critical step that facilitates AKT membrane recruitment, phosphorylation, and subsequent activation of downstream signaling such as the GSK3β/β-catenin axis, ultimately promoting epithelial–mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also underscores the potential clinical importance of JMJD8 in cancer. Initially identified as a cancer-related gene in a pan-cancer analysis, further studies have revealed that in hepatocellular carcinoma, JMJD8 is upregulated in cells resistant to Lenvatinib—a first-line therapeutic agent. Here, JMJD8 functions in concert with USP22 to enhance stem cell-like properties, invasion, and overall drug resistance, thereby indicating that JMJD8 may serve as a promising therapeutic target to improve the efficacy of both radio- and chemotherapy in treating tumors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kok Siong Yeo, Ming Cheang Tan, Yat-Yuen Lim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JMJD8 is a novel endoplasmic reticulum protein with a JmjC domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-15676-z"}], "href": "https://doi.org/10.1038/s41598-017-15676-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29133832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29133832"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yao Su, Jun Wang "}, {"type": "b", "children": [{"type": "t", "text": "JmjC domain-containing protein 8 (JMJD8) represses Ku70/Ku80 expression via attenuating AKT/NF-κB/COX-2 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2019.118541"}], "href": "https://doi.org/10.1016/j.bbamcr.2019.118541"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31473257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31473257"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yao Su, Xueying Wang, Zhen Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant JmjC domain-containing protein 8 (JMJD8) expression promotes activation of AKT and tumor epithelial-mesenchymal transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-020-01446-1"}], "href": "https://doi.org/10.1038/s41388-020-01446-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32879443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32879443"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xisong Liang, Hao Zhang, Zeyu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JMJD8 Is an M2 Macrophage Biomarker, and It Associates With DNA Damage Repair to Facilitate Stemness Maintenance, Chemoresistance, and Immunosuppression in Pan-Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2022.875786"}], "href": "https://doi.org/10.3389/fimmu.2022.875786"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35898493"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35898493"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jinhui Guo, Jie Zhao "}, {"type": "b", "children": [{"type": "t", "text": "USP22-JMJD8 axis promotes Lenvatinib resistance in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2023.119617"}], "href": "https://doi.org/10.1016/j.bbamcr.2023.119617"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37898375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37898375"}]}]}]}