|
|
|
| Research progress on the function of lysine-specific demethylase 1 |
| QIN Xuke1 WU Yingguang2 ZHONG Guangqing2 GUO Ji2 WANG Lei1 DU Yang1 CHEN Zhiyuan1 LIU Xiuheng1 |
1.Department of Urology, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China;
2.the First Department of Surgery, Hai’nan Changjiang Medical Group, Hai’nan Province, Changjiang 572700, China |
|
|
|
Abstract Histone lysine-specific demethylase 1 （LSD1） can catalyze the demethylation of mono-or di-methyl-lysine 4 or 9 of histone H3 for regulating gene expression. Through its demethylation function, LSD1 is involved in a variety of cellular activities in human body, such as cell proliferation, epithelial-mesenchymal transition, autophagy, etc. More and more studies have shown that its abnormal expression is associated with the occurrence, development and poor prognosis of a variety of cancers and other diseases, and LSD1 is a key regulatory factor. As a result, a number of drugs targeting LSD1 are being studied in clinical trials. Howerer, most of these inhibitors are based on blocking their demethylase activity. Recent studies show that LSD1 is also involved in a series of protein-protein interactions that are independent of its demethylation function. This greatly expands the scope of its biological function and provides new strategies and directions for the design of LSD1 inhibitors. Based on the current literatures, this paper summarize the research progress of function of LSD1 and discuss its application prospect.
|
|
|
|
|
|
[1] Hosseini A，Minucci S. A comprehensive review of lysine-specific demethylase 1 and its roles in cancer [J]. Epigenomics，2017，9（8）：1123-1142.
[2] Shi Y，Lan F，Matson C，et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 [J]. Cell，2004，119（7）：941-953.
[3] Magliulo D，Bernardi R，Messina S. Lysine-Specific Demethylase 1A as a Promising Target in Acute Myeloid Leukemia [J]. Front Oncol，2018，8：255.
[4] Huang J，Sengupta R，Espejo AB，et al. p53 is regulated by the lysine demethylase LSD1 [J]. Nature，2007，449（7158）：105-108.
[5] He Y，Zhao Y，Wang L，et al. LSD1 promotes S-phase entry and tumorigenesis via chromatin co-occupation with E2F1 and selective H3K9 demethylation [J]. Oncogene，2018，37（4）：534-543.
[6] Zhang J，Yuan B，Zhang F，et al. Cyclophosphamide perturbs cytosine methylation in Jurkat-T cells through LSD1-mediated stabilization of DNMT1 protein [J]. Chem Res Toxicol，2011，24（11）：2040-2043.
[7] Lee JY，Park JH，Choi HJ，et al. LSD1 demethylates HIF1alpha to inhibit hydroxylation and ubiquitin-mediated degradation in tumor angiogenesis [J]. Oncogene，2017，36（39）：5512-5521.
[8] Yang J，Huang J，Dasgupta M，et al. Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes [J]. P Natl Acad Sci Usa，2010，107（50）：21499-21504.
[9] Yang GJ，Lei PM，Wong SY，et al. Pharmacological Inhibition of LSD1 for Cancer Treatment [J]. Molecules，2018， 23（12）：20.
[10] Ambrosio S，Saccà CD，Majello B. Epigenetic regulation of epithelial to mesenchymal transition by the Lysine-specific demethylase LSD1/KDM1A [J]. Bba-gene Regul Mech，2017，1860（9）：905-910.
[11] Ambrosio S，Ballabio A，Majello B. Histone methyl-transferases and demethylases in the autophagy regulatory network：the emerging role of KDM1A/LSD1 demethylase [J]. Autophagy，2019，15（2）：187-196.
[12] Gulyaeva O，Dempersmier J，Sul HS. Genetic and epigenetic control of adipose development [J]. Bba-mol Cell Biol L，2019，1864（1）：3-12.
[13] Yan HJ，Zhou SY，Li Y，et al. The effects of LSD1 inhibition on self-renewal and differentiation of human induced pluripotent stem cells [J]. Exp Cell Res，2016，340（2）：227-237.
[14] Whyte WA，Bilodeau S，Orlando DA，et al. Enhancer decommissioning by LSD1 during embryonic stem cell differentiation [J]. Nature，2012，482（7384）：221-225.
[15] Karakaidos P，Verigos J，Magklara A. LSD1/KDM1A，a Gate-Keeper of Cancer Stemness and a Promising Therapeutic Target [J]. Cancers （Basel），2019，11（12）：21.
[16] Gu F，Lin Y，Wang Z，et al. Biological roles of LSD1 beyond its demethylase activity [J]. Cell Mol Life Sci，2020：10.
[17] Zheng YC，Ma J，Wang Z，et al. A Systematic Review of Histone Lysine-Specific Demethylase 1 and Its Inhibitors [J]. Med Res Rev，2015，35（5）：1032-1071.
[18] Hwang I，Cao D，Na Y，et al. Far Upstream Element-Binding Protein 1 Regulates LSD1 Alternative Splicing to Promote Terminal Differentiation of Neural Progenitors [J]. Stem Cell Rep，2018，10（4）：1208-1221.
[19] Rusconi F，Grillo B，Toffolo E，et al. NeuroLSD1：Splicing-Generated Epigenetic Enhancer of Neuroplasticity [J]. Trends Neurosci，2017，40（1）：28-38.
[20] Majello B，Gorini F，Saccà CD，et al. Expanding the role of the histone lysine-specific demethylase lsd1 in cancer [J]. Cancers （basel），2019，11（3）：15.
[21] Bhan A，Mandal SS. LncRNA HOTAIR：A master regulator of chromatin dynamics and cancer [J]. Biochim Biophys Acta，2015，1856（1）：151-164.
[22] Porro A，Feuerhahn S，Lingner J. TERRA-Reinforced Association of LSD1 with MRE11 Promotes Processing of Uncapped Telomeres [J]. Cell Rep，2014，6（4）：765-776.
[23] Beato M，Vicent GP. A new role for an old player：steroid receptor RNA Activator （SRA） represses hormone inducible genes [J]. Transcription，2013，4（4）：167-171.
[24] Huang M，Hou J，Wang Y，et al. Long Noncoding RNA LINC00673 Is Activated by SP1 and Exerts Oncogenic Properties by Interacting with LSD1 and EZH2 in Gastric Cancer [J]. Mol Ther，2017，25（4）：1014-1026.
[25] Xu TP，Wang WY，Ma P，et al. Upregulation of the long noncoding RNA FOXD2-AS1 promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1，and predicts poor prognosis in gastric cancer [J]. Oncogene，2018，37（36）：5020-5036.
[26] Peng F，Shi X，Meng Y，et al. Long non-coding RNA HOTTIP is upregulated in renal cell carcinoma and regulates cell growth and apoptosis by epigenetically silencing of LATS2 [J]. Biomed Pharmacother，2018，105：1133-1140.
[27] Zhang X，Tanaka K，Yan J，et al. Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation [J]. P Natl Acad Sci Usa，2013， 110（43）：17284-17289.
[28] Sheng W，LaFleur MW，Nguyen TH，et al. LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade[J]. Cell，2018；174（3）：549-563，e519.
[29] Cho HS，Suzuki T，Dohmae N，et al. Demethylation of RB regulator MYPT1 by histone demethylase LSD1 promotes cell cycle progression in cancer cells [J]. Cancer Res，2011，71（3）：655-660.
[30] Metzger E，Wissmann M，Yin N，et al. LSD1 demethylates repressive histone marks to promote androgen-receptor- dependent transcription [J]. Nature，2005，437（7057）：436-439.
[31] Sehrawat A. LSD1 activates a lethal prostate cancer gene network independently of its demethylase function [J]. Cancer Res，2018，78（13）：E4179-E4188.
[32] Chao A，Lin CY，Chao AN，et al. Lysine-specific demethylase 1 （LSD1） destabilizes p62 and inhibits autophagy in gynecologic malignancies [J]. Oncotarget，2017，8（43）：74434-74450.
[33] Moscat J，Diaz-Meco MT. p62 at the Crossroads of Autophagy，Apoptosis，and Cancer [J]. Cell，2009，137（6）：1001-1004.
[34] Carnesecchi J，Cerutti C，Vanacker JM，et al. ERRα protein is stabilized by LSD1 in a demethylation-independent manner [J]. PLoS One，2017，12（11）：12.
[35] Horard B，Vanacker JM. Estrogen receptor-related receptors：Orphan receptors desperately seeking a ligand [J]. J Mol Endocrinol，2003，31（3）：349-357.
[36] Lan H，Tan M，Zhang Q，et al. LSD1 destabilizes FBXW7 and abrogates FBXW7 functions independent of its demethylase activity [J]. P Natl Acad Sci Usa，2019，116（25）：12311-12320.
[37] Welcker M，Clurman BE. FBW7 ubiquitin ligase：A tumour suppressor at the crossroads of cell division，growth and differentiation [J]. Nat Rev Cancer，2008，8（2）：83-93. |
|
|
|
