{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DIO3OS is a long non‐coding RNA transcribed in antisense orientation to the Dio3 gene that has emerged as an important regulator of thyroid hormone homeostasis and cellular differentiation, with context‐dependent roles in metabolism, reproduction, and tumorigenesis. In metabolic tissues, DIO3OS—in contrast to its partner Dio3—appears to counteract thyroid hormone inactivation. For example, in fetal brown adipose tissue maternal obesity suppresses DIO3OS leading to increased Dio3 expression, intracellular triiodothyronine (T3) deficiency, and impaired thermogenesis; conversely, gain‐of‐function experiments indicate that DIO3OS reduces D3 levels and enhances brown adipose tissue activity, protecting against diet‐induced obesity (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the reproductive context, DIO3OS is coordinately expressed with Dio3 during decidualization, where it fine‐tunes the expression of the deiodinase to modulate local T3 availability essential for stromal cell differentiation in early pregnancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer and inflammatory diseases, DIO3OS expression is frequently dysregulated. Several studies have reported its downregulation in aggressive endometrial cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", inflammatory bowel disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", and cervical cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In hepatocellular carcinoma and non‐small cell lung cancer, alterations in DIO3OS expression have been linked to aberrant ceRNA networks and epigenetic repression, suggesting that DIO3OS may function as a tumor suppressor by modulating key signaling pathways such as Hedgehog."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In contrast, in thyroid carcinoma elevated DIO3OS expression is associated with poorer overall survival and appears to promote malignancy via a regulatory axis involving let‐7d and NF‐κB2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, DIO3OS has been identified as a potential target of chromatin regulators such as EZH2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and it resides within prognostic ceRNA networks in hepatocellular carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "as well as in endometrial and intrauterine adhesion disease networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, genetic variants in DIO3OS have been associated with increased anemia risk, underscoring its role in intracellular thyroid hormone regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that DIO3OS is a multifunctional lncRNA that modulates thyroid hormone inactivation and fine‐tunes cellular responses in endocrine, metabolic, reproductive, and tumor contexts. Its dysregulation not only affects local T3 bioavailability and tissue development but also contributes to disease pathogenesis through its involvement in complex ceRNA and epigenetic networks."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yan-Ting Chen, Qi-Yuan Yang, Yun Hu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Regulation and function of deiodinases during decidualization in female mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2014-1015"}], "href": "https://doi.org/10.1210/en.2014-1015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24797630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24797630"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Peixin Dong, Ying Xiong, Junming Yue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA NEAT1 drives aggressive endometrial cancer progression via miR-361-regulated networks involving STAT3 and tumor microenvironment-related genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-019-1306-9"}], "href": "https://doi.org/10.1186/s13046-019-1306-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31287002"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31287002"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sen Wang, Yong Hou, Weiping Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KIF9‑AS1, LINC01272 and DIO3OS lncRNAs as novel biomarkers for inflammatory bowel disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2017.8118"}], "href": "https://doi.org/10.3892/mmr.2017.8118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29207070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29207070"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anirban Roychowdhury, Sudip Samadder, Pijush Das, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deregulation of H19 is associated with cervical carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2019.06.012"}], "href": "https://doi.org/10.1016/j.ygeno.2019.06.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31229557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31229557"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhanpeng Wang, Lina Song, Yanshuo Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long Noncoding RNA DIO3OS Hinders Cell Malignant Behaviors of Hepatocellular Carcinoma Cells Through the microRNA-328/Hhip Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Manag Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/CMAR.S245990"}], "href": "https://doi.org/10.2147/CMAR.S245990"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32547226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32547226"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Meichun Zhang, Jing Wu, Weinong Zhong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-methylation-induced silencing of DIO3OS drives non-small cell lung cancer progression via activating hnRNPK-MYC-CDC25A axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther Oncolytics (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.omto.2021.09.006"}], "href": "https://doi.org/10.1016/j.omto.2021.09.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34761103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34761103"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mingming Wang, Jin Li, Zhongkun Zuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA DIO3OS/let-7d/NF-κB2 axis regulates cells proliferation and metastasis of thyroid cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Commun Signal (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12079-020-00589-w"}], "href": "https://doi.org/10.1007/s12079-020-00589-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33058043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33058043"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yuan Li, Mei Luo, Xuejiao Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated bioinformatics analysis of chromatin regulator EZH2 in regulating mRNA and lncRNA expression by ChIP sequencing and RNA sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.13169"}], "href": "https://doi.org/10.18632/oncotarget.13169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27835578"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27835578"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Cheng Zhang, Tianhao Bao, Yang Ke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated analysis of ceRNA network reveals potential prognostic Hint1-related lncRNAs involved in hepatocellular carcinoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Surg Oncol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12957-022-02535-z"}], "href": "https://doi.org/10.1186/s12957-022-02535-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35241097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35241097"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jingni Zhang, Peng Jiang, Yuan Tu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and validation of long non-coding RNA associated ceRNAs in intrauterine adhesion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.2017578"}], "href": "https://doi.org/10.1080/21655979.2021.2017578"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34968168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34968168"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Nicolien A van Vliet, Annelies E P Kamphuis, Wendy P J den Elzen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thyroid Function and Risk of Anemia: A Multivariable-Adjusted and Mendelian Randomization Analysis in the UK Biobank."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/clinem/dgab674"}], "href": "https://doi.org/10.1210/clinem/dgab674"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34514498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34514498"}]}]}]}