组蛋白去甲基化酶 JMJD1A 的缺氧诱导因子 1α调控增强缺氧基因表达和肿瘤生长。
Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth.
机构信息
Division of Radiation and Cancer Biology, Department of Radiation Oncology, Center for Clinical Sciences Research, Stanford University, Stanford, CA 94303-5152, USA.
出版信息
Mol Cell Biol. 2010 Jan;30(1):344-53. doi: 10.1128/MCB.00444-09.
Abstract
The hypoxia-inducible transcription factors (HIFs) directly and indirectly mediate cellular adaptation to reduced oxygen tensions. Recent studies have shown that the histone demethylase genes JMJD1A, JMJD2B, and JARID1B are HIF targets, suggesting that HIFs indirectly influence gene expression at the level of histone methylation under hypoxia. In this study, we identify a subset of hypoxia-inducible genes that are dependent on JMJD1A in both renal cell and colon carcinoma cell lines. JMJD1A regulates the expression of adrenomedullin (ADM) and growth and differentiation factor 15 (GDF15) under hypoxia by decreasing promoter histone methylation. In addition, we demonstrate that loss of JMJD1A is sufficient to reduce tumor growth in vivo, demonstrating that histone demethylation plays a significant role in modulating growth within the tumor microenvironment. Thus, hypoxic regulation of JMJD1A acts as a signal amplifier to facilitate hypoxic gene expression, ultimately enhancing tumor growth.
摘要
缺氧诱导转录因子 (HIFs) 直接或间接介导细胞对低氧张力的适应。最近的研究表明，组蛋白去甲基化酶基因 JMJD1A、JMJD2B 和 JARID1B 是 HIF 的靶标，这表明 HIFs 在低氧条件下通过组蛋白甲基化水平间接影响基因表达。在这项研究中，我们在肾细胞和结肠癌细胞系中确定了一组依赖于 JMJD1A 的缺氧诱导基因。JMJD1A 通过降低启动子组蛋白甲基化来调节缺氧条件下肾上腺髓质素 (ADM) 和生长分化因子 15 (GDF15) 的表达。此外，我们证明 JMJD1A 的缺失足以减少体内肿瘤的生长，表明组蛋白去甲基化在调节肿瘤微环境中的生长中起着重要作用。因此，JMJD1A 的缺氧调节作用充当信号放大器，促进缺氧基因表达，最终增强肿瘤生长。
相似文献
1
Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth.组蛋白去甲基化酶 JMJD1A 的缺氧诱导因子 1α调控增强缺氧基因表达和肿瘤生长。
Mol Cell Biol. 2010 Jan;30(1):344-53. doi: 10.1128/MCB.00444-09.
2
The expression of histone demethylase JMJD1A in renal cell carcinoma.组蛋白去甲基化酶 JMJD1A 在肾细胞癌中的表达。
Neoplasma. 2011;58(2):153-7. doi: 10.4149/neo_2011_02_153.
3
4
The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF.组蛋白去甲基化酶JMJD1A和JMJD2B是缺氧诱导因子HIF的转录靶点。
J Biol Chem. 2008 Dec 26;283(52):36542-52. doi: 10.1074/jbc.M804578200. Epub 2008 Nov 4.
5
Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1α.组蛋白去甲基酶 JMJD1A 通过与缺氧诱导因子 1α 共激活增强糖酵解促进膀胱癌进展。
Oncogene. 2017 Jul 6;36(27):3868-3877. doi: 10.1038/onc.2017.13. Epub 2017 Mar 6.
6
The hypoxia-inducible factor-α prolyl hydroxylase inhibitor FG4592 ameliorates renal fibrosis by inducing the H3K9 demethylase JMJD1A.缺氧诱导因子-α脯氨酰羟化酶抑制剂FG4592通过诱导H3K9去甲基化酶JMJD1A改善肾纤维化。
Am J Physiol Renal Physiol. 2022 Nov 1;323(5):F539-F552. doi: 10.1152/ajprenal.00083.2022. Epub 2022 Sep 8.
7
The histone demethylase JMJD1A regulates adrenomedullin-mediated cell proliferation in hepatocellular carcinoma under hypoxia.组蛋白去甲基化酶 JMJD1A 在低氧环境下调节肾上腺髓质素介导的肝癌细胞增殖。
Biochem Biophys Res Commun. 2013 May 17;434(4):722-7. doi: 10.1016/j.bbrc.2013.03.091. Epub 2013 Apr 10.
8
HIF-1α-induced histone demethylase JMJD2B contributes to the malignant phenotype of colorectal cancer cells via an epigenetic mechanism.HIF-1α 诱导的组蛋白去甲基酶 JMJD2B 通过表观遗传机制促进结直肠癌细胞的恶性表型。
Carcinogenesis. 2012 Sep;33(9):1664-73. doi: 10.1093/carcin/bgs217. Epub 2012 Jun 27.
9
Hypoxia causes epigenetic gene regulation in macrophages by attenuating Jumonji histone demethylase activity.缺氧通过减弱 Jumonji 组蛋白去甲基化酶活性来调节巨噬细胞中的表观遗传基因调控。
Cytokine. 2011 Feb;53(2):256-62. doi: 10.1016/j.cyto.2010.11.002. Epub 2010 Dec 4.
10
Hypoxia and nickel inhibit histone demethylase JMJD1A and repress Spry2 expression in human bronchial epithelial BEAS-2B cells.缺氧和镍抑制人支气管上皮 BEAS-2B 细胞中的组蛋白去甲基酶 JMJD1A 并抑制 Spry2 的表达。
Carcinogenesis. 2010 Dec;31(12):2136-44. doi: 10.1093/carcin/bgq197. Epub 2010 Sep 29.
引用本文的文献
1
Silencing Calumenin Expression via Artificial MicroRNA, a Potential Breakthrough for Inhibiting Proliferation, Halting Migration, and Triggering Apoptosis in Breast Cancer Cells.通过人工微小RNA沉默钙网蛋白表达，这是抑制乳腺癌细胞增殖、阻止迁移和触发凋亡的潜在突破。
Adv Pharm Bull. 2025 Jun 11;15(2):453-466. doi: 10.34172/apb.025.43819. eCollection 2025 Jul.
2
Maternal iron deficiency causes male-to-female sex reversal in mouse embryos.母体缺铁会导致小鼠胚胎出现雄性向雌性的性逆转。
Nature. 2025 Jun 4. doi: 10.1038/s41586-025-09063-2.
3
The Distinct Role of HIF-1α and HIF-2α in Hypoxia and Angiogenesis.缺氧诱导因子-1α（HIF-1α）和缺氧诱导因子-2α（HIF-2α）在缺氧和血管生成中的不同作用
Cells. 2025 May 4;14(9):673. doi: 10.3390/cells14090673.
4
Endometrium-derived organoids from cystic fibrosis patients and mice as new models to study disease-associated endometrial pathobiology.来自囊性纤维化患者和小鼠的子宫内膜来源类器官作为研究疾病相关子宫内膜病理生物学的新模型。
Cell Mol Life Sci. 2025 Mar 13;82(1):109. doi: 10.1007/s00018-025-05627-7.
5
KDM5C and KDM5D mutations have different consequences in clear cell renal cell carcinoma cells.KDM5C和KDM5D突变在肾透明细胞癌细胞中具有不同的后果。
Commun Biol. 2025 Feb 15;8(1):244. doi: 10.1038/s42003-025-07695-8.
6
Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer.矛盾基因的发现：重新评估癌症中过表达基因的预后影响。
Front Cell Dev Biol. 2025 Jan 22;13:1525345. doi: 10.3389/fcell.2025.1525345. eCollection 2025.
7
Impact of Hypoxia and the Levels of Transcription Factor HIF-1α and JMJD1A on Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Cell Lines.缺氧和转录因子 HIF-1α 及 JMJD1A 水平对头颈部鳞状细胞癌细胞系上皮-间充质转化的影响。
Cancer Genomics Proteomics. 2024 Nov-Dec;21(6):591-607. doi: 10.21873/cgp.20476.
8
Reorganization of H3K9me heterochromatin leads to neuronal impairment via the cascading destruction of the KDM3B-centered epigenomic network.H3K9me异染色质的重组通过以KDM3B为中心的表观基因组网络的级联破坏导致神经元损伤。
iScience. 2024 Jun 26;27(8):110380. doi: 10.1016/j.isci.2024.110380. eCollection 2024 Aug 16.
9
The emerging roles of histone demethylases in cancers.组蛋白去甲基化酶在癌症中的新兴作用。
Cancer Metastasis Rev. 2024 Jun;43(2):795-821. doi: 10.1007/s10555-023-10160-9. Epub 2024 Jan 16.
10
Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype.肿瘤缺氧反应的纵向动力学：从酶活性到生物学表型。
Sci Adv. 2023 Nov 24;9(47):eadj6409. doi: 10.1126/sciadv.adj6409. Epub 2023 Nov 22.
本文引用的文献
1
Molecular basis of coiled coil coactivator recruitment by the aryl hydrocarbon receptor nuclear translocator (ARNT).芳烃受体核转运蛋白（ARNT）招募卷曲螺旋共激活因子的分子基础。
J Biol Chem. 2009 May 29;284(22):15184-92. doi: 10.1074/jbc.M808479200. Epub 2009 Mar 26.
2
Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis.缺氧诱导因子（HIF）结合与反式激活的综合分析揭示了其在维持组蛋白甲基化稳态中的作用。
Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4260-5. doi: 10.1073/pnas.0810067106. Epub 2009 Mar 2.
3
Role of Jhdm2a in regulating metabolic gene expression and obesity resistance.Jhdm2a在调节代谢基因表达和抗肥胖中的作用。
Nature. 2009 Apr 9;458(7239):757-61. doi: 10.1038/nature07777. Epub 2009 Feb 4.
4
The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF.组蛋白去甲基化酶JMJD1A和JMJD2B是缺氧诱导因子HIF的转录靶点。
J Biol Chem. 2008 Dec 26;283(52):36542-52. doi: 10.1074/jbc.M804578200. Epub 2008 Nov 4.
5
Kinase requirements in human cells: III. Altered kinase requirements in VHL-/- cancer cells detected in a pilot synthetic lethal screen.人类细胞中的激酶需求：III. 在初步合成致死筛选中检测到的VHL-/-癌细胞中激酶需求的改变
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16484-9. doi: 10.1073/pnas.0806574105. Epub 2008 Oct 23.
6
Regulation of Jumonji-domain-containing histone demethylases by hypoxia-inducible factor (HIF)-1alpha.缺氧诱导因子（HIF）-1α对含Jumonji结构域的组蛋白去甲基化酶的调控
Biochem J. 2008 Dec 15;416(3):387-94. doi: 10.1042/BJ20081238.
7
Up-regulation of the hypoxia-inducible factor-1 transcriptional pathway in colorectal carcinomas.结直肠癌中缺氧诱导因子-1转录途径的上调
Hum Pathol. 2008 Oct;39(10):1483-94. doi: 10.1016/j.humpath.2008.02.013. Epub 2008 Jul 11.
8
A molecule targeting VHL-deficient renal cell carcinoma that induces autophagy.一种靶向诱导自噬的VHL缺陷型肾细胞癌的分子。
Cancer Cell. 2008 Jul 8;14(1):90-102. doi: 10.1016/j.ccr.2008.06.004.
9
Hypoxia upregulates the histone demethylase JMJD1A via HIF-1.缺氧通过低氧诱导因子-1上调组蛋白去甲基化酶JMJD1A。
Biochem Biophys Res Commun. 2008 Aug 8;372(4):892-7. doi: 10.1016/j.bbrc.2008.05.150. Epub 2008 Jun 4.
10
Involvement of estrogen-related receptors in transcriptional response to hypoxia and growth of solid tumors.雌激素相关受体在实体瘤对缺氧的转录反应及生长中的作用。
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7821-6. doi: 10.1073/pnas.0711677105. Epub 2008 May 28.
Zotero 插件