DIO3

Last update 08 May 2025

Basic Info

Synonyms

5DIII, deiodinase, iodothyronine type III, DIO3

+ [8]

Introduction

Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development.

100 Clinical Results associated with DIO3

100 Translational Medicine associated with DIO3

0 Patents (Medical) associated with DIO3

760

Literatures (Medical) associated with DIO3

01 Dec 2025·Functional & Integrative Genomics

Transcriptome analysis of the hypothalamus and testes in Brandt’s Vole: new insights into mechanisms of photoperiodic plasticity in postnatal testicular development

Article

Author: Liu, Xiao-Hui ; Ying, Yaqi ; Zhao, Lijuan ; Li, Ning ; Wang, Lewen ; Song, Ying ; Wang, Dawei ; Wang, Zhenlong ; Sun, Hong

Postnatal gonadal development is regulated by photoperiod via the hypothalamus, especially in seasonal breeding small rodents. However, the precise molecular mechanisms remain unclear. In this study, we conducted a comparative analysis of the transcriptomes of the hypothalamus and testes in 10-week-old male Brandt's voles born under long (LP, 16L:8D) and short photoperiod (SP, 8L:16D) conditions. Results indicate that the SP group exhibited significantly smaller testes with spermatogenesis halted before meiosis, identifying 129 differentially expressed genes (DEGs) in the hypothalamus and 21,673 DEGs in the testes. In the hypothalamus, genes involved in the thyroid hormone and retinoic acid (RA) pathway were notably altered under SP conditions, including decreased Tshb and Cga expression, increased Dio3, and reduced Crabp1 and Lrat, highlighting their key roles in SP signaling. In the testes, downregulated genes were significantly enriched in male reproduction-related GO terms and metabolic KEGG pathways, such as steroid hormone biosynthesis and retinol metabolism. Key genes for testosterone synthesis (e.g. Star, Cyp11a1) and RA synthesis (e.g. Rdh10, Rdh11) were downregulated, while those linked to RA degradation (Cyp26b1) and undifferentiated spermatogonia maintenance (e.g. Gdnf, Gfra1) were upregulated. These findings outline a molecular microenvironment that favors the preservation of undifferentiated spermatogonia over their differentiation from the hypothalamus to the testes. This study firstly provides valuable insights into the transcriptomic basis of SP-inhibited testicular development in Brandt's voles.

01 Aug 2025·Tissue and Cell

Rotenone-driven DNA hypermethylation of the miR-6991–3p promoter induces death of mouse brain organoids

Article

Author: Gao, Xijin ; Cui, Zeyu ; Liu, Te ; Liu, Xin ; Yu, Zhihua ; Pan, Weidong

Rotenone has potential chemical toxicity in the nervous system of both insects and mammals, but its deep molecular biological mechanisms have not been clarified. Here, the epigenetic regulatory mechanism underlying the toxicity of rotenone was studied using murine brain organoids (mBOs). Transmission electron microscopy indicated that rotenone destroyed mBOs'mitochondrial structure. RRBS-Seq showed that some promoter regions from the DLK1-DIO3 imprinted microRNA clusters were hypomethylated. But, rotenone stimulated hypermethylation significantly on the promoter DNA of miR-6991-3p. MiR-6991-3p in the rotenone-treated mBOs had the greatest decreased miRNA expression compared with the control. Meanwhile, luciferase report assay indicated that miR-6991-3p induced a decrease in luciferase activity via binding to specific sites on the 3'UTR of DEDD2 gene. To overexpression of miR-6991-3p attenuated mBO proliferated inhibition and cell death, accumulation for lipid peroxidation products significantly by rotenone inducing. Subsequently, results of cell staining and molecular biology experiment revealed that overexpression for miR-6991-3p significantly weakened expression levels of death-related genes (DEDD2, caspase-8, caspase-3, and caspase-1), but significantly elevated expression levels of cell proliferation-related genes (Ki67 and BCL2) in rotenone treated mBOs group. Here, we reveal a novel epigenetic mechanism of rotenone-induced neuronal death, in which rotenone induced promoter DNA hypermethylation of miR-6991-3p in the DLK1-DIO3 imprinted cluster. This caused miR-6991-3p transcriptional activity to be downregulated, which subsequently significantly increased the expression of its target gene, DEDD2, ultimately leading to neural organoid cell death.

01 Jun 2025·Molecular Immunology

MicroRNA-770 promotes polarization of macrophages and hemorrhoids by suppressing RYBP expression and monoubiquitination of histone H2A on Lys119 modification

Article

Author: Liu, Te ; Yang, Wei ; Zhou, Haikun ; Zhong, Shenglan

Hemorrhoid disease (HD) is a common proctological condition whose onset is associated with an abnormal inflammatory microenvironment; however, the underlying mechanisms remain unclear. In this study, pathological examination revealed a significant increase in MΦ1 macrophages in the hemorrhoidal tissue of patients with HD, along with elevated levels of inflammatory factors. qPCR results demonstrated that the expression of several members of the DLK1-DIO3 microRNA cluster, particularly miR-770, was significantly higher in the hemorrhoid tissue of patients with HD than in that of the control group. Luciferase reporter assays confirmed that RYBP is a target gene negatively regulated by miR-770. Additionally, qPCR and western blot analyses indicated that overexpression of miR-770 significantly downregulated the expression of PRC1 family genes and RYBP in THP-1 cells, while concurrently upregulating the expression of inflammatory factors such as NFKB, IL1b, IL4, TNF, and IFNG. The overexpression of miR-770 significantly induced the polarization of THP-1 cells toward MΦ1. Mechanistic studies using ChIP-seq revealed that miR-770 overexpression significantly reduced the number of gene promoters in MΦ1 cells that bind to histone H2AK119-Ub sites. Furthermore, the number of enriched DNA fragments from genes that bind to the + 1 transcription start site of histone H2AK119-Ub, such as NFKB1, IL1B, and TNF, was significantly lower than that observed in the control group. Therefore, we confirmed that miR-770, a genomic imprinted member of the DLK1-DIO3 region, negatively regulated the expression of the PRC1 family member RYBP, reduced the level of ubiquitination modification at histone H2AK119-Ub, and promoted the transcriptional activation of pro-inflammatory genes. This ultimately leads to MΦ1 polarization and the release of inflammatory factors, elucidating the epigenetic mechanisms underlying the occurrence of hemorrhoids.

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DIO3

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