{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts explicitly describe MIR5089, the collective evidence paints a picture of how epigenetic regulators—chiefly the H3K9‐specific demethylases such as JMJD1A (also known as KDM3A/JHDM2A)—orchestrate critical developmental and cellular programs. In pluripotent embryonic stem cells and during early embryogenesis, JMJD1A is under transcriptional control by key factors such as OCT4 and STAT3, and it contributes to the maintenance of stem cell identity and reprogramming capacity by demethylating silencing marks on histone H3 lysine 9. Moreover, its role in spermatogenesis is underscored by regulatory functions that include activating transition nuclear protein and protamine genes essential for chromatin condensation, and its loss leads to infertility and cytoplasmic abnormalities in maturing sperm."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond development, these studies reveal that JMJD1A/KDM3A integrates tissue‐ and context‐dependent signals to regulate gene expression in metabolic and stress‐responsive processes. In metabolic tissues such as brown adipose tissue and skeletal muscle, JMJD1A is activated by β‑adrenergic signaling and phosphorylated to act both as a scaffold for chromatin remodeling and as an enzyme that directly removes repressive histone modifications, thereby inducing thermogenic and lipid oxidation gene programs. Its roles extend to modulating energy expenditure, autophagy in the liver, and even influencing cardiac function where microRNA networks (for example, miR‑216a‑5p and miR‑30a‑5p) and long noncoding RNAs like HOTAIR modulate its expression and activity—mechanisms that are also implicated in conditions ranging from neuropathic pain and metabolic syndrome to chronic heart failure. Additionally, exploration of modulatory microRNAs (as in the case of miR‑194 in vascular disorders) further highlights the interplay between noncoding RNAs and histone demethylase–driven epigenetic programs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA further layer of regulation is uncovered in the context of oncogenesis and cytoskeletal dynamics. In several cancer models and under conditions of hypoxic stress, alterations in JMJD1A activity—whether via direct inhibition by nitric oxide and iron sequestration or due to genetic variation affecting its mRNA structure—can either suppress or promote tumor growth, depending on the cellular context and the complement of interacting proteins such as AP‑1 or the SWI/SNF complex. In vascular smooth muscle differentiation and other specialized cellular functions, JMJD1A interacts with transcriptional co‑activators (for instance, members of the myocardin family) to fine‑tune gene expression programs. Together, these integrated studies emphasize that while MIR5089 is not directly addressed, the functional axes mediated by JMJD1A and its regulation by various microRNAs and noncoding elements may serve as a conceptual parallel, suggesting that similar regulatory motifs—including one potentially mediated by MIR5089—could modulate epigenetic landscapes in both normal physiology and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julia Knebel, Luciano De Haro, Ralf Janknecht "}, {"type": "b", "children": [{"type": "t", "text": "Repression of transcription by TSGA/Jmjd1a, a novel interaction partner of the ETS protein ER71."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.20945"}], "href": "https://doi.org/10.1002/jcb.20945"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16619273"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16619273"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Song Yi Ko, Hye Yoon Kang, Hyun Sil Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of Jmjd1a as a STAT3 downstream gene in mES cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Struct Funct (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1247/csf.31.53"}], "href": "https://doi.org/10.1247/csf.31.53"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16988490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16988490"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuin-Han Loh, Weiwei Zhang, Xi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1588207"}], "href": "https://doi.org/10.1101/gad.1588207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17938240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17938240"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuki Okada, Greg Scott, Manas K Ray, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06236"}], "href": "https://doi.org/10.1038/nature06236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17943087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17943087"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kashelle Lockman, Joan M Taylor, Christopher P Mack "}, {"type": "b", "children": [{"type": "t", "text": "The histone demethylase, Jmjd1a, interacts with the myocardin factors to regulate SMC differentiation marker gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.107.164178"}], "href": "https://doi.org/10.1161/CIRCRESAHA.107.164178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17991879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17991879"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Dengke K Ma, Cheng-Hsuan J Chiang, Karthikeyan Ponnusamy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1634/stemcells.2008-0388"}], "href": "https://doi.org/10.1634/stemcells.2008-0388"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18535151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18535151"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Keisuke Tateishi, Yuki Okada, Eric M Kallin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Jhdm2a in regulating metabolic gene expression and obesity resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature07777"}], "href": "https://doi.org/10.1038/nature07777"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19194461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19194461"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Takeshi Inagaki, Makoto Tachibana, Kenta Magoori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Obesity and metabolic syndrome in histone demethylase JHDM2a-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2443.2009.01326.x"}], "href": "https://doi.org/10.1111/j.1365-2443.2009.01326.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19624751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19624751"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yuki Okada, Keisuke Tateishi, Yi Zhang "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylase JHDM2A is involved in male infertility and obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Androl (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2164/jandrol.109.008052"}], "href": "https://doi.org/10.2164/jandrol.109.008052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19875498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19875498"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zhaoliang Liu, Suoling Zhou, Lan Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Jmjd1a demethylase-regulated histone modification is essential for cAMP-response element modulator-regulated gene expression and spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.066845"}], "href": "https://doi.org/10.1074/jbc.M109.066845"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19910458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19910458"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yohei Abe, Royhan Rozqie, Yoshihiro Matsumura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms8052"}], "href": "https://doi.org/10.1038/ncomms8052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25948511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25948511"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Shunsuke Kuroki, Yuji Nakai, Ryo Maeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Reports (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stemcr.2018.02.002"}], "href": "https://doi.org/10.1016/j.stemcr.2018.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29526734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29526734"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yohei Abe, Yosuke Fujiwara, Hiroki Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03868-8"}], "href": "https://doi.org/10.1038/s41467-018-03868-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29674659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29674659"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Zhantao Tian, Lv Yao, Yongqing Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone H3K9 demethylase JMJD1A is a co-activator of erythropoietin expression under hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2019.01.022"}], "href": "https://doi.org/10.1016/j.biocel.2019.01.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30716474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30716474"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Rongjia Zang, Qingyun Tan, Fanrong Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JMJD1A Represses the Development of Cardiomyocyte Hypertrophy by Regulating the Expression of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Catalase"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2020/5081323"}], "href": "https://doi.org/10.1155/2020/5081323"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32461996"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32461996"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Joomyung Kim, Seon Ah Choi, Jaebeom Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lysine-specific demethylase 3A is important for autophagic occurrence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2020.03.058"}], "href": "https://doi.org/10.1016/j.bbrc.2020.03.058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32201075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32201075"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Xiaoyun Zhang, Yakun Gao, Hongyu Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOX transcript antisense RNA mitigates cardiac function injury in chronic heart failure via regulating microRNA-30a-5p to target KDM3A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.17160"}], "href": "https://doi.org/10.1111/jcmm.17160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35083842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35083842"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Hua Zhang, Yanfang Wang, Xiaolei Bian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-194 acts as a suppressor during abdominal aortic aneurysm via inhibition of KDM3A-mediated BNIP3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2021.119309"}], "href": "https://doi.org/10.1016/j.lfs.2021.119309"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33662431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33662431"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jason R Hickok, Divya Vasudevan, William E Antholine, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nitric oxide modifies global histone methylation by inhibiting Jumonji C domain-containing demethylases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.432294"}], "href": "https://doi.org/10.1074/jbc.M112.432294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23546878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23546878"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Shunsuke Kuroki, Shogo Matoba, Mika Akiyoshi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic regulation of mouse sex determination by the histone demethylase Jmjd1a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1239864"}], "href": "https://doi.org/10.1126/science.1239864"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24009392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24009392"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Alan Gillett, Petra Bergman, Roham Parsa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A silent exonic SNP in kdm3a affects nucleic acids structure but does not regulate experimental autoimmune encephalomyelitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0081912"}], "href": "https://doi.org/10.1371/journal.pone.0081912"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24312603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24312603"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Ioannis Kasioulis, Heather M Syred, Peri Tate, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kdm3a lysine demethylase is an Hsp90 client required for cytoskeletal rearrangements during spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E13-08-0471"}], "href": "https://doi.org/10.1091/mbc.E13-08-0471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24554764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24554764"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Jun Ueda, Jolene Caifeng Ho, Kian Leong Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hypoxia-inducible epigenetic regulators Jmjd1a and G9a provide a mechanistic link between angiogenesis and tumor growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00099-14"}], "href": "https://doi.org/10.1128/MCB.00099-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25071150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25071150"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "T Nakatsuka, K Tateishi, Y Kudo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2017.222"}], "href": "https://doi.org/10.1038/onc.2017.222"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28692045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28692045"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Lingling Fan, Khadka Sudeep, Jianfei Qi "}, {"type": "b", "children": [{"type": "t", "text": "Histone Demethylase KDM3 (JMJD1) in Transcriptional Regulation and Cancer Progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Exp Med Biol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-3-031-38176-8_4"}], "href": "https://doi.org/10.1007/978-3-031-38176-8_4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37751136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37751136"}]}]}]}