Skip to content
2000
Volume 25, Issue 8
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Epigenetic alterations are implicated in the early stages of tumorigenesis and are widely recognized as a ubiquitous phenomenon in cancer development. Aberrant epigenetic modifications can alter the expression of target genes, induce heterochromatin formation, and gradually drive normal cells towards immortalized tumor cells with significant consequences. SETDB1 (SET domain bifurcated histone lysine methyltransferase 1), a typical histone methyltransferase, promotes the formation of heterochromatin and inhibits the transcription of genes by modifying the methylation of lysine 9 of histone 3. SETDB1 is usually highly expressed in tumors with high copy numbers, accompanied by poor prognosis and low patient survival rates, which is a typical case of abnormal epigenetic modification. We discuss the mechanism of SETDB1 in a variety of cancers and review the epigenetic inhibitors that have been reported in recent years, along with their anti-tumor effects. In addition, we summarize the role of SETDB1 in a variety of diseases and cell functions.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ccdt/10.2174/0115680096311909240721160523
2024-08-27
2025-10-23

  • From This Site

    /content/journals/ccdt/10.2174/0115680096311909240721160523
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. GoldbergA.D. AllisC.D. BernsteinE. Epigenetics: a landscape takes shape.Cell2007128463563810.1016/j.cell.2007.02.00617320500
     [Google Scholar]
  2. BirdA. Perceptions of epigenetics.Nature2007447714339639810.1038/nature0591317522671
     [Google Scholar]
  3. HashimotoH. VertinoP.M. ChengX. Molecular coupling of DNA methylation and histone methylation.Epigenomics20102565766910.2217/epi.10.4421339843
     [Google Scholar]
  4. RyuH.Y. HochstrasserM. Histone sumoylation and chromatin dynamics.Nucleic Acids Res.202149116043605210.1093/nar/gkab28033885816
     [Google Scholar]
  5. LykoF. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation.Nat. Rev. Genet.2018192819210.1038/nrg.2017.8029033456
     [Google Scholar]
  6. YooC.B. JonesP.A. Epigenetic therapy of cancer: past, present and future.Nat. Rev. Drug Discov.200651375010.1038/nrd193016485345
     [Google Scholar]
  7. ZelicR. FianoV. GrassoC. ZugnaD. PetterssonA. Gillio-TosA. MerlettiF. RichiardiL. Global DNA hypomethylation in prostate cancer development and progression: a systematic review.Prostate Cancer Prostatic Dis.201518111210.1038/pcan.2014.4525384337
     [Google Scholar]
  8. LeeT.J. YuanX. KerrK. YooJ.Y. KimD.H. KaurB. EltzschigH.K. Strategies to Modulate MicroRNA Functions for the Treatment of Cancer or Organ Injury.Pharmacol. Rev.202072363966710.1124/pr.119.01902632554488
     [Google Scholar]
  9. SaitoY. HibinoS. SaitoH. Alterations of epigenetics and micro RNA in hepatocellular carcinoma.Hepatol. Res.2014441314210.1111/hepr.1214723617364
     [Google Scholar]
  10. CarrollA.P. GoodallG.J. LiuB. Understanding principles of miRNA target recognition and function through integrated biological and bioinformatics approaches.Wiley Interdiscip. Rev. RNA20145336137910.1002/wrna.121724459110
     [Google Scholar]
  11. KrolJ. LoedigeI. FilipowiczW. The widespread regulation of microRNA biogenesis, function and decay.Nat. Rev. Genet.201011959761010.1038/nrg284320661255
     [Google Scholar]
  12. Miranda FurtadoC.L. Dos Santos LucianoM.C. Silva SantosR.D. FurtadoG.P. MoraesM.O. PessoaC. Epidrugs: targeting epigenetic marks in cancer treatment.Epigenetics201914121164117610.1080/15592294.2019.164054631282279
     [Google Scholar]
  13. GreerE.L. ShiY. Histone methylation: a dynamic mark in health, disease and inheritance.Nat. Rev. Genet.201213534335710.1038/nrg317322473383
     [Google Scholar]
  14. ShanmugamM.K. ArfusoF. ArumugamS. ChinnathambiA. JinsongB. WarrierS. WangL.Z. KumarA.P. AhnK.S. SethiG. LakshmananM. Role of novel histone modifications in cancer.Oncotarget2018913114141142610.18632/oncotarget.2335629541423
     [Google Scholar]
  15. Millán-ZambranoG. BurtonA. BannisterA.J. SchneiderR. Histone post-translational modifications — cause and consequence of genome function.Nat. Rev. Genet.202223956358010.1038/s41576‑022‑00468‑735338361
     [Google Scholar]
  16. TanM. LuoH. LeeS. JinF. YangJ.S. MontellierE. BuchouT. ChengZ. RousseauxS. RajagopalN. LuZ. YeZ. ZhuQ. WysockaJ. YeY. KhochbinS. RenB. ZhaoY. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification.Cell201114661016102810.1016/j.cell.2011.08.00821925322
     [Google Scholar]
  17. SabariB.R. TangZ. HuangH. Yong-GonzalezV. MolinaH. KongH.E. DaiL. ShimadaM. CrossJ.R. ZhaoY. RoederR.G. AllisC.D. Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation.Mol. Cell201558220321510.1016/j.molcel.2015.02.02925818647
     [Google Scholar]
  18. ByvoetP. ShepherdG.R. HardinJ.M. NolandB.J. The distribution and turnover of labeled methyl groups in histone fractions of cultured mammalian cells.Arch. Biochem. Biophys.1972148255856710.1016/0003‑9861(72)90174‑95063076
     [Google Scholar]
  19. SkvortsovaK. IovinoN. BogdanovićO. Functions and mechanisms of epigenetic inheritance in animals.Nat. Rev. Mol. Cell Biol.2018191277479010.1038/s41580‑018‑0074‑230425324
     [Google Scholar]
  20. ChenD. MaH. HongH. KohS.S. HuangS.M. SchurterB.T. AswadD.W. StallcupM.R. Regulation of transcription by a protein methyltransferase.Science199928454232174217710.1126/science.284.5423.217410381882
     [Google Scholar]
  21. ReaS. EisenhaberF. O’CarrollD. StrahlB.D. SunZ.W. SchmidM. OpravilS. MechtlerK. PontingC.P. AllisC.D. JenuweinT. Regulation of chromatin structure by site-specific histone H3 methyltransferases.Nature2000406679659359910.1038/3502050610949293
     [Google Scholar]
  22. FengQ. WangH. NgH.H. Erdjument-BromageH. TempstP. StruhlK. ZhangY. Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.Curr. Biol.200212121052105810.1016/S0960‑9822(02)00901‑612123582
     [Google Scholar]
  23. HerzH.M. GarrussA. ShilatifardA. SET for life: biochemical activities and biological functions of SET domain-containing proteins.Trends Biochem. Sci.2013381262163910.1016/j.tibs.2013.09.00424148750
     [Google Scholar]
  24. SchultzD.C. AyyanathanK. NegorevD. MaulG.G. RauscherF.J.III SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins.Genes Dev.200216891993210.1101/gad.97330211959841
     [Google Scholar]
  25. TachibanaM. SugimotoK. NozakiM. UedaJ. OhtaT. OhkiM. FukudaM. TakedaN. NiidaH. KatoH. ShinkaiY. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis.Genes Dev.200216141779179110.1101/gad.98940212130538
     [Google Scholar]
  26. TachibanaM. UedaJ. FukudaM. TakedaN. OhtaT. IwanariH. SakihamaT. KodamaT. HamakuboT. ShinkaiY. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9.Genes Dev.200519781582610.1101/gad.128400515774718
     [Google Scholar]
  27. BlackJ.C. Van RechemC. WhetstineJ.R. Histone lysine methylation dynamics: establishment, regulation, and biological impact.Mol. Cell201248449150710.1016/j.molcel.2012.11.00623200123
     [Google Scholar]
  28. García-CaoM. O’SullivanR. PetersA.H.F.M. JenuweinT. BlascoM.A. Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases.Nat. Genet.2004361949910.1038/ng127814702045
     [Google Scholar]
  29. LoyolaA. TagamiH. BonaldiT. RocheD. QuivyJ.P. ImhofA. NakataniY. DentS.Y.R. AlmouzniG. The HP1α–CAF1–SetDB1‐containing complex provides H3K9me1 for Suv39‐mediated K9me3 in pericentric heterochromatin.EMBO Rep.200910776977510.1038/embor.2009.9019498464
     [Google Scholar]
  30. SunL. FangJ. E3-Independent Constitutive Monoubiquitination Complements Histone Methyltransferase Activity of SETDB1.Mol. Cell201662695896610.1016/j.molcel.2016.04.02227237050
     [Google Scholar]
  31. IshimotoK. KawamataN. UchiharaY. OkuboM. FujimotoR. GotohE. KakinouchiK. MizohataE. HinoN. OkadaY. MochizukiY. TanakaT. HamakuboT. SakaiJ. KodamaT. InoueT. TachibanaK. DoiT. Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity.PLoS One20161110e016576610.1371/journal.pone.016576627798683
     [Google Scholar]
  32. BathamJ. LimP.S. RaoS. SETDB-1: A Potential Epigenetic Regulator in Breast Cancer Metastasis.Cancers (Basel)2019118114310.3390/cancers1108114331405032
     [Google Scholar]
  33. LiL. ChenB.F. ChanW.Y. An epigenetic regulator: methyl-CpG-binding domain protein 1 (MBD1).Int. J. Mol. Sci.20151635125514010.3390/ijms1603512525751725
     [Google Scholar]
  34. ChenK. ZhangF. DingJ. LiangY. ZhanZ. ZhanY. ChenL. DingY. Histone Methyltransferase SETDB1 Promotes the Progression of Colorectal Cancer by Inhibiting the Expression of TP53.J. Cancer20178163318333010.7150/jca.2048229158805
     [Google Scholar]
  35. LawsonK.A. TeteakC.J. GaoJ. LiN. HacquebordJ. GhatanA. Zielinska-KwiatkowskaA. SongG. ChanskyH.A. YangL. ESET histone methyltransferase regulates osteoblastic differentiation of mesenchymal stem cells during postnatal bone development.FEBS Lett.2013587243961396710.1016/j.febslet.2013.10.02824188826
     [Google Scholar]
  36. ChenC. NottT.J. JinJ. PawsonT. Deciphering arginine methylation: Tudor tells the tale.Nat. Rev. Mol. Cell Biol.2011121062964210.1038/nrm318521915143
     [Google Scholar]
  37. YangL. MeiQ. Zielinska-KwiatkowskaA. MatsuiY. BlackburnM.L. BenedettiD. KrummA.A. TaborskyG.J.Jr ChanskyH.A. An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B.Biochem. J.2003369365165710.1042/bj2002085412398767
     [Google Scholar]
  38. FriedmanJ.R. FredericksW.J. JensenD.E. SpeicherD.W. HuangX.P. NeilsonE.G. RauscherF.J.III KAP-1, a novel corepressor for the highly conserved KRAB repression domain.Genes Dev.199610162067207810.1101/gad.10.16.20678769649
     [Google Scholar]
  39. SripathyS.P. StevensJ. SchultzD.C. The KAP1 corepressor functions to coordinate the assembly of de novo HP1-demarcated microenvironments of heterochromatin required for KRAB zinc finger protein-mediated transcriptional repression.Mol. Cell. Biol.200626228623863810.1128/MCB.00487‑0616954381
     [Google Scholar]
  40. IvanovA.V. PengH. YurchenkoV. YapK.L. NegorevD.G. SchultzD.C. PsulkowskiE. FredericksW.J. WhiteD.E. MaulG.G. SadofskyM.J. ZhouM.M. RauscherF.J.III PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing.Mol. Cell200728582383710.1016/j.molcel.2007.11.01218082607
     [Google Scholar]
  41. ChoS. ParkJ.S. KangY.K. Dual functions of histone-lysine N-methyltransferase Setdb1 protein at promyelocytic leukemia-nuclear body (PML-NB): maintaining PML-NB structure and regulating the expression of its associated genes.J. Biol. Chem.201128647411154112410.1074/jbc.M111.24853421921037
     [Google Scholar]
  42. DellaireG. ChingR.W. AhmedK. JalaliF. TseK.C.K. BristowR.G. Bazett-JonesD.P. Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR.J. Cell Biol.20061751556610.1083/jcb.20060400917030982
     [Google Scholar]
  43. KaranthA.V. ManiswamiR.R. PrashanthS. GovindarajH. PadmavathyR. JegatheesanS.K. MullangiR. RajagopalS. Emerging role of SETDB1 as a therapeutic target.Expert Opin. Ther. Targets201721331933110.1080/14728222.2017.127960428076698
     [Google Scholar]
  44. ChaseK.A. GavinD.P. GuidottiA. SharmaR.P. Histone methylation at H3K9: Evidence for a restrictive epigenome in schizophrenia.Schizophr. Res.20131491-3152010.1016/j.schres.2013.06.02123815974
     [Google Scholar]
  45. CukierH.N. LeeJ.M. MaD. YoungJ.I. MayoV. ButlerB.L. RamsookS.S. RantusJ.A. AbramsA.J. WhiteheadP.L. WrightH.H. AbramsonR.K. HainesJ.L. CuccaroM.L. Pericak-VanceM.A. GilbertJ.R. The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1.Autism Res.20125638539710.1002/aur.125123055267
     [Google Scholar]
  46. MatsuiT. LeungD. MiyashitaH. MaksakovaI.A. MiyachiH. KimuraH. TachibanaM. LorinczM.C. ShinkaiY. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET.Nature2010464729092793110.1038/nature0885820164836
     [Google Scholar]
  47. BilodeauS. KageyM.H. FramptonG.M. RahlP.B. YoungR.A. SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state.Genes Dev.200923212484248910.1101/gad.183730919884255
     [Google Scholar]
  48. AndjelkovićM. AlessiD.R. MeierR. FernandezA. LambN.J.C. FrechM. CronP. CohenP. LucocqJ.M. HemmingsB.A. Role of translocation in the activation and function of protein kinase B.J. Biol. Chem.199727250315153152410.1074/jbc.272.50.315159395488
     [Google Scholar]
  49. De GraeveF. BahrA. ChattonB. KedingerC. A murine ATFa-associated factor with transcriptional repressing activity.Oncogene200019141807181910.1038/sj.onc.120349210777215
     [Google Scholar]
  50. WadeP.A. Methyl CpG binding proteins: coupling chromatin architecture to gene regulation.Oncogene200120243166317310.1038/sj.onc.120434011420733
     [Google Scholar]
  51. SharmaP. Hu-LieskovanS. WargoJ.A. RibasA. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.Cell2017168470772310.1016/j.cell.2017.01.01728187290
     [Google Scholar]
  52. BurrM.L. SparbierC.E. ChanK.L. ChanY.C. KersbergenA. LamE.Y.N. Azidis-YatesE. VassiliadisD. BellC.C. GilanO. JacksonS. TanL. WongS.Q. HollizeckS. MichalakE.M. SiddleH.V. McCabeM.T. PrinjhaR.K. GuerraG.R. SolomonB.J. SandhuS. DawsonS.J. BeavisP.A. TothillR.W. CullinaneC. LehnerP.J. SutherlandK.D. DawsonM.A. An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.Cancer Cell2019364385401.e810.1016/j.ccell.2019.08.00831564637
     [Google Scholar]
  53. GoltzD. GevenslebenH. GrünenS. DietrichJ. KristiansenG. LandsbergJ. DietrichD. PD-L1 (CD274) promoter methylation predicts survival in patients with acute myeloid leukemia.Leukemia201731373874310.1038/leu.2016.32827840427
     [Google Scholar]
  54. MicevicG. ThakralD. McGearyM. BosenbergM.W. PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival.Pigment Cell Melanoma Res.201932343544010.1111/pcmr.1274530343532
     [Google Scholar]
  55. LadleB.H. LiK.P. PhillipsM.J. PucsekA.B. HaileA. PowellJ.D. JaffeeE.M. HildemanD.A. GamperC.J. De novo DNA methylation by DNA methyltransferase 3a controls early effector CD8 + T-cell fate decisions following activation.Proc. Natl. Acad. Sci. USA201611338106311063610.1073/pnas.152449011327582468
     [Google Scholar]
  56. YuB. ZhangK. MilnerJ.J. TomaC. ChenR. Scott-BrowneJ.P. PereiraR.M. CrottyS. ChangJ.T. PipkinM.E. WangW. GoldrathA.W. Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation.Nat. Immunol.201718557358210.1038/ni.370628288100
     [Google Scholar]
  57. MicevicG. BosenbergM.W. YanQ. The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy.Clin. Cancer Res.20232971173118210.1158/1078‑0432.CCR‑22‑078436449280
     [Google Scholar]
  58. ZhangS.M. CaiW.L. LiuX. ThakralD. LuoJ. ChanL.H. McGearyM.K. SongE. BlenmanK.R.M. MicevicG. JesselS. ZhangY. YinM. BoothC.J. JilaveanuL.B. DamskyW. SznolM. KlugerH.M. IwasakiA. BosenbergM.W. YanQ. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements.Nature2021598788268268710.1038/s41586‑021‑03994‑234671158
     [Google Scholar]
  59. LinJ. GuoD. LiuH. ZhouW. WangC. MüllerI. KossenkovA.V. DrapkinR. BitlerB.G. HelinK. ZhangR. The SETDB1–TRIM28 Complex Suppresses Antitumor Immunity.Cancer Immunol. Res.20219121413142410.1158/2326‑6066.CIR‑21‑075434848497
     [Google Scholar]
  60. GriffinG.K. WuJ. Iracheta-VellveA. PattiJ.C. HsuJ. DavisT. Dele-OniD. DuP.P. HalawiA.G. IshizukaJ.J. KimS.Y. KlaegerS. KnudsenN.H. MillerB.C. NguyenT.H. OlanderK.E. PapanastasiouM. RachimiS. RobitschekE.J. SchneiderE.M. YearyM.D. ZimmerM.D. JaffeJ.D. CarrS.A. DoenchJ.G. HainingW.N. YatesK.B. MangusoR.T. BernsteinB.E. Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity.Nature2021595786630931410.1038/s41586‑021‑03520‑433953401
     [Google Scholar]
  61. TakikitaS. MuroR. TakaiT. OtsuboT. KawamuraY.I. DohiT. OdaH. KitajimaM. OshimaK. HattoriM. EndoT.A. ToyodaT. WeisJ. ShinkaiY. SuzukiH. A Histone Methyltransferase ESET Is Critical for T Cell Development.J. Immunol.201619762269227910.4049/jimmunol.150248627511731
     [Google Scholar]
  62. PasquarellaA. EbertA. de AlmeidaG.P. HinterbergerM. KazeraniM. NuberA. EllwartJ. KleinL. BusslingerM. SchottaG. Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro-B cells.Development201614310dev.13020310.1242/dev.13020327013243
     [Google Scholar]
  63. YangW.H. HeithoffD.M. AzizP.V. SperandioM. NizetV. MahanM.J. MarthJ.D. Recurrent infection progressively disables host protection against intestinal inflammation.Science20173586370eaao561010.1126/science.aao561029269445
     [Google Scholar]
  64. LuoH. WuX. ZhuX.H. YiX. DuD. JiangD.S. The functions of SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) in biological process and disease.Epigenetics Chromatin20231614710.1186/s13072‑023‑00519‑138057834
     [Google Scholar]
  65. WangR. LiH. WuJ. CaiZ.Y. LiB. NiH. QiuX. ChenH. LiuW. YangZ.H. LiuM. HuJ. LiangY. LanP. HanJ. MoW. Gut stem cell necroptosis by genome instability triggers bowel inflammation.Nature2020580780338639010.1038/s41586‑020‑2127‑x32296174
     [Google Scholar]
  66. ChenL. DaiM. ZuoW. DaiY. YangQ. YuS. HuangM. LiuH. NF-κB p65 and SETDB1 expedite lipopolysaccharide-induced intestinal inflammation in mice by inducing IRF7/NLR-dependent macrophage M1 polarization.Int. Immunopharmacol.202311510955410.1016/j.intimp.2022.10955436580757
     [Google Scholar]
  67. HachiyaR. ShiihashiT. ShirakawaI. IwasakiY. MatsumuraY. OishiY. NakayamaY. MiyamotoY. ManabeI. OchiK. TanakaM. GodaN. SakaiJ. SuganamiT. OgawaY. The H3K9 methyltransferase Setdb1 regulates TLR4-mediated inflammatory responses in macrophages.Sci. Rep.2016612884510.1038/srep2884527349785
     [Google Scholar]
  68. XiaK. WangT. ChenZ. GuoJ. YuB. ChenQ. QiuT. ZhouJ. ZhengS. Hepatocellular SETDB1 regulates hepatic ischemia-reperfusion injury through targeting lysine methylation of ASK1 Signal.Research2023625610.34133/research.0256
     [Google Scholar]
  69. JužnićL. PeukerK. StrigliA. BroschM. HerrmannA. HäslerR. KochM. MatthiesenL. ZeissigY. LöscherB.S. NuberA. SchottaG. NeumeisterV. ChavakisT. KurthT. LescheM. DahlA. von MässenhausenA. LinkermannA. SchreiberS. AdenK. RosenstielP.C. FrankeA. HampeJ. ZeissigS. SETDB1 is required for intestinal epithelial differentiation and the prevention of intestinal inflammation.Gut202170348549810.1136/gutjnl‑2020‑32133932503845
     [Google Scholar]
  70. HaoH. QiH. RatnamM. Modulation of the folate receptor type β gene by coordinate actions of retinoic acid receptors at activator Sp1/ets and repressor AP-1 sites.Blood2003101114551456010.1182/blood‑2002‑10‑317412543860
     [Google Scholar]
  71. NaH.H. KimK.C. SETDB1-mediated FosB regulation via ERK2 is associated with an increase in cell invasiveness during anticancer drug treatment of A549 human lung cancer cells.Biochem. Biophys. Res. Commun.2018495151251810.1016/j.bbrc.2017.10.17629108991
     [Google Scholar]
  72. MengX. XiaoW. SunJ. LiW. YuanH. YuT. ZhangX. DongW. CircPTK2/PABPC1/SETDB1 axis promotes EMT-mediated tumor metastasis and gemcitabine resistance in bladder cancer.Cancer Lett.202355421602310.1016/j.canlet.2022.21602336436682
     [Google Scholar]
  73. LiuZ. LiuJ. EbrahimiB. PratapU.P. HeY. AltweggK.A. TangW. LiX. LaiZ. ChenY. ShenL. SareddyG.R. ViswanadhapalliS. TekmalR.R. RaoM.K. VadlamudiR.K. SETDB1 interactions with PELP1 contributes to breast cancer endocrine therapy resistance.Breast Cancer Res.20222412610.1186/s13058‑022‑01520‑435395812
     [Google Scholar]
  74. HouZ. SunL. XuF. HuF. LanJ. SongD. FengY. WangJ. LuoX. HuJ. WangG. Blocking histone methyltransferase SETDB1 inhibits tumorigenesis and enhances cetuximab sensitivity in colorectal cancer.Cancer Lett.2020487637310.1016/j.canlet.2020.05.02932473242
     [Google Scholar]
  75. LuoF. ZhangM. SunB. XuC. YangY. ZhangY. LiS. ChenG. ChenC. LiY. FengH. LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling.Mol. Cancer20242316010.1186/s12943‑024‑01975‑338520019
     [Google Scholar]
  76. LeeJ.H. KimE.W. CroteauD.L. BohrV.A. Heterochromatin: an epigenetic point of view in aging.Exp. Mol. Med.20205291466147410.1038/s12276‑020‑00497‑432887933
     [Google Scholar]
  77. ZhangW. QuJ. LiuG.H. BelmonteJ.C.I. The ageing epigenome and its rejuvenation.Nat. Rev. Mol. Cell Biol.202021313715010.1038/s41580‑019‑0204‑532020082
     [Google Scholar]
  78. PalS. TylerJ.K. Epigenetics and aging.Sci. Adv.201627e160058410.1126/sciadv.160058427482540
     [Google Scholar]
  79. StrepkosD. MarkouliM. KlonouA. PapavassiliouA.G. PiperiC. Histone Methyltransferase SETDB1: A Common Denominator of Tumorigenesis with Therapeutic Potential.Cancer Res.202181352553410.1158/0008‑5472.CAN‑20‑290633115801
     [Google Scholar]
  80. ManningB.D. CantleyL.C. AKT/PKB signaling: navigating downstream.Cell200712971261127410.1016/j.cell.2007.06.00917604717
     [Google Scholar]
  81. FilippaN. SableC.L. HemmingsB.A. Van ObberghenE. Effect of phosphoinositide-dependent kinase 1 on protein kinase B translocation and its subsequent activation.Mol. Cell. Biol.200020155712572110.1128/MCB.20.15.5712‑5721.200010891507
     [Google Scholar]
  82. HillM.M. FengJ. HemmingsB.A. Identification of a plasma membrane Raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1.Curr. Biol.200212141251125510.1016/S0960‑9822(02)00973‑912176337
     [Google Scholar]
  83. Martinez CalejmanC. TrefelyS. EntwisleS.W. LucianoA. JungS.M. HsiaoW. TorresA. HungC.M. LiH. SnyderN.W. VillénJ. WellenK.E. GuertinD.A. mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis.Nat. Commun.202011157510.1038/s41467‑020‑14430‑w31996678
     [Google Scholar]
  84. HanS. ZhenW. GuoT. ZouJ. LiF. RETRACTED ARTICLE: SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway.J. Exp. Clin. Cancer Res.202039121810.1186/s13046‑020‑01730‑833059737
     [Google Scholar]
  85. HuaF. TianY. GaoY. LiC. LiuX. Colony‑stimulating factor 1 receptor inhibition blocks macrophage infiltration and endometrial cancer cell proliferation.Mol. Med. Rep.20191943139314710.3892/mmr.2019.996330816518
     [Google Scholar]
  86. WangG. LongJ. GaoY. ZhangW. HanF. XuC. SunL. YangS.C. LanJ. HouZ. CaiZ. JinG. HsuC.C. WangY.H. HuJ. ChenT.Y. LiH. LeeM.G. LinH.K. SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis.Nat. Cell Biol.201921221422510.1038/s41556‑018‑0266‑130692626
     [Google Scholar]
  87. AlessiD.R. JamesS.R. DownesC.P. HolmesA.B. GaffneyP.R.J. ReeseC.B. CohenP. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα.Curr. Biol.19977426126910.1016/S0960‑9822(06)00122‑99094314
     [Google Scholar]
  88. CaoN. YuY. ZhuH. ChenM. ChenP. ZhuoM. MaoY. LiL. ZhaoQ. WuM. YeM. SETDB1 promotes the progression of colorectal cancer via epigenetically silencing p21 expression.Cell Death Dis.202011535110.1038/s41419‑020‑2561‑632393761
     [Google Scholar]
  89. LiuT. ChenX. LiT. LiX. LyuY. FanX. ZhangP. ZengW. Histone methyltransferase SETDB1 maintains survival of mouse spermatogonial stem/progenitor cells via PTEN/AKT/FOXO1 pathway.Biochim. Biophys. Acta. Gene Regul. Mech.20171860101094110210.1016/j.bbagrm.2017.08.00928890329
     [Google Scholar]
  90. MorikawaM. DerynckR. MiyazonoK. TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology.Cold Spring Harb. Perspect. Biol.201685a02187310.1101/cshperspect.a02187327141051
     [Google Scholar]
  91. LamouilleS. XuJ. DerynckR. Molecular mechanisms of epithelial–mesenchymal transition.Nat. Rev. Mol. Cell Biol.201415317819610.1038/nrm375824556840
     [Google Scholar]
  92. ChenG. DengC. LiY.P. TGF-β and BMP signaling in osteoblast differentiation and bone formation.Int. J. Biol. Sci.20128227228810.7150/ijbs.292922298955
     [Google Scholar]
  93. ShiC. YuanY. GuoY. JingJ. HoT.V. HanX. LiJ. FengJ. ChaiY. BMP Signaling in Regulating Mesenchymal Stem Cells in Incisor Homeostasis.J. Dent. Res.201998890491110.1177/002203451985081231136721
     [Google Scholar]
  94. HuL. ChengZ. WuL. LuoL. PanP. LiS. JiaQ. YangN. XuB. Histone methyltransferase SETDB1 promotes osteogenic differentiation in osteoporosis by activating OTX2-mediated BMP-Smad and Wnt/β-catenin pathways.Hum. Cell20233641373138810.1007/s13577‑023‑00902‑w37074626
     [Google Scholar]
  95. ShibueT. WeinbergR.A. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications.Nat. Rev. Clin. Oncol.2017141061162910.1038/nrclinonc.2017.4428397828
     [Google Scholar]
  96. LamouilleS. ConnollyE. SmythJ.W. AkhurstR.J. DerynckR. TGF-β-induced activation of mTOR complex 2 drives epithelial–mesenchymal transition and cell invasion.J. Cell Sci.201212551259127310.1242/jcs.09529922399812
     [Google Scholar]
  97. DuD. KatsunoY. MeyerD. BudiE.H. ChenS.H. KoeppenH. WangH. AkhurstR.J. DerynckR. Smad3‐mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial–mesenchymal transition.EMBO Rep.201819113515510.15252/embr.20174425029233829
     [Google Scholar]
  98. RyuT.Y. KimK. KimS.K. OhJ.H. MinJ.K. JungC.R. SonM.Y. KimD.S. ChoH.S. SETDB1 regulates SMAD7 expression for breast cancer metastasis.BMB Rep.201952213914410.5483/BMBRep.2019.52.2.23530545440
     [Google Scholar]
  99. WuP.C. LuJ.W. YangJ.Y. LinI.H. OuD.L. LinY.H. ChouK.H. HuangW.F. WangW.P. HuangY.L. HsuC. LinL.I. LinY.M. ShenC.K.J. TzengT.Y. H3K9 histone methyltransferase, KMT1E/SETDB1, cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis.Cancer Res.201474247333734310.1158/0008‑5472.CAN‑13‑357225477335
     [Google Scholar]
  100. ShangW. WangY. LiangX. LiT. ShaoW. LiuF. CuiX. WangY. LvL. ChaiL. QuL. ZhengL. JiaJ. SETDB1 promotes gastric carcinogenesis and metastasis via upregulation of CCND1 and MMP9 expression.J. Pathol.2021253214815910.1002/path.556833044755
     [Google Scholar]
  101. XuL. LiaoW.L. LuQ.J. ZhangP. ZhuJ. JiangG.N. RETRACTED: Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma.Mol. Ther. Nucleic Acids2021231078109210.1016/j.omtn.2021.01.01933614250
     [Google Scholar]
  102. ZhangY. HuangJ. LiQ. ChenK. LiangY. ZhanZ. YeF. NiW. ChenL. DingY. Histone methyltransferase SETDB1 promotes cells proliferation and migration by interacting withTiam1 in hepatocellular carcinoma.BMC Cancer201818153910.1186/s12885‑018‑4464‑929739365
     [Google Scholar]
  103. HuangJ. YeX. GuanJ. ChenB. LiQ. ZhengX. LiuL. WangS. DingY. DingY. ChenL. Tiam1 is associated with hepatocellular carcinoma metastasis.Int. J. Cancer201313219010010.1002/ijc.2762722573407
     [Google Scholar]
  104. MochizukiK. TandoY. SekinakaT. OtsukaK. HayashiY. KobayashiH. KamioA. Ito-MatsuokaY. TakeharaA. KonoT. OsumiN. MatsuiY. SETDB1 is essential for mouse primordial germ cell fate determination by ensuring BMP signaling.Development201814523dev16416010.1242/dev.16416030446626
     [Google Scholar]
  105. BroshR. RotterV. When mutants gain new powers: news from the mutant p53 field.Nat. Rev. Cancer200991070171310.1038/nrc269319693097
     [Google Scholar]
  106. HsuI.C. MetcalfR.A. SunT. WelshJ.A. WangN.J. HarrisC.C. Mutational hot spot in the p53 gene in human hepatocellular carcinomas.Nature1991350631742742810.1038/350427a01849234
     [Google Scholar]
  107. MullerP.A.J. VousdenK.H. Mutant p53 in cancer: new functions and therapeutic opportunities.Cancer Cell201425330431710.1016/j.ccr.2014.01.02124651012
     [Google Scholar]
  108. FeiQ. ShangK. ZhangJ. ChuaiS. KongD. ZhouT. FuS. LiangY. LiC. ChenZ. ZhaoY. YuZ. HuangZ. HuM. YingH. ChenZ. ZhangY. XingF. ZhuJ. XuH. ZhaoK. LuC. AtadjaP. XiaoZ.X. LiE. ShouJ. Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53.Nat. Commun.201561865110.1038/ncomms965126471002
     [Google Scholar]
  109. LiuL. KimballS. LiuH. HolowatyjA. YangZ.Q. Genetic alterations of histone lysine methyltransferases and their significance in breast cancer.Oncotarget2015642466248210.18632/oncotarget.296725537518
     [Google Scholar]
  110. YuH. LeeH. HerrmannA. BuettnerR. JoveR. Revisiting STAT3 signalling in cancer: new and unexpected biological functions.Nat. Rev. Cancer2014141173674610.1038/nrc381825342631
     [Google Scholar]
  111. ZouS. TongQ. LiuB. HuangW. TianY. FuX. Targeting STAT3 in Cancer Immunotherapy.Mol. Cancer202019114510.1186/s12943‑020‑01258‑732972405
     [Google Scholar]
  112. ZhangH. CaiK. WangJ. WangX. ChengK. ShiF. JiangL. ZhangY. DouJ. MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway.Stem Cells201432112858286810.1002/stem.179525070049
     [Google Scholar]
  113. NaH.H. MoonS. KimK.C. Knockout of SETDB1 gene using the CRISPR/cas-9 system increases migration and transforming activities via complex regulations of E-cadherin, β-catenin, STAT3, and Akt.Biochem. Biophys. Res. Commun.2020533348649210.1016/j.bbrc.2020.09.02632972752
     [Google Scholar]
  114. YuL. YeF. LiY.Y. ZhanY.Z. LiuY. YanH.M. FangY. XieY.W. ZhangF.J. ChenL.H. DingY. ChenK.L. Histone methyltransferase SETDB1 promotes colorectal cancer proliferation through the STAT1-CCND1/CDK6 axis.Carcinogenesis202041567868810.1093/carcin/bgz13131306481
     [Google Scholar]
  115. XiaoJ.F. SunQ.Y. DingL.W. ChienW. LiuX.Y. MayakondaA. JiangY.Y. LohX.Y. RanX.B. DoanN.B. CastorB. ChiaD. SaidJ.W. TanK.T. YangH. FuX.Y. LinD.C. KoefflerH.P. The c‐MYC–BMI1 axis is essential for SETDB1‐mediated breast tumourigenesis.J. Pathol.201824618910210.1002/path.512629926931
     [Google Scholar]
  116. JohnsonD.E. O’KeefeR.A. GrandisJ.R. Targeting the IL-6/JAK/STAT3 signalling axis in cancer.Nat. Rev. Clin. Oncol.201815423424810.1038/nrclinonc.2018.829405201
     [Google Scholar]
  117. GoldsteinB. TakeshitaH. MizumotoK. SawaH. Wnt signals can function as positional cues in establishing cell polarity.Dev. Cell200610339139610.1016/j.devcel.2005.12.01616516841
     [Google Scholar]
  118. LohK.M. van AmerongenR. NusseR. Generating Cellular Diversity and Spatial Form: Wnt Signaling and the Evolution of Multicellular Animals.Dev. Cell201638664365510.1016/j.devcel.2016.08.01127676437
     [Google Scholar]
  119. McMahonA.P. JoynerA.L. BradleyA. McMahonJ.A. The midbrain-hindbrain phenotype of Wnt-1−Wnt-1− mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum.Cell199269458159510.1016/0092‑8674(92)90222‑X1534034
     [Google Scholar]
  120. StarkK. VainioS. VassilevaG. McMahonA.P. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4.Nature1994372650767968310.1038/372679a07990960
     [Google Scholar]
  121. SunQ.Y. DingL.W. XiaoJ.F. ChienW. LimS.L. HattoriN. GoodglickL. ChiaD. MahV. AlaviM. KimS.R. DoanN.B. SaidJ.W. LohX.Y. XuL. LiuL.Z. YangH. HayanoT. ShiS. XieD. LinD.C. KoefflerH.P. SETDB1 accelerates tumourigenesis by regulating the WNT signalling pathway.J. Pathol.2015235455957010.1002/path.448225404354
     [Google Scholar]
  122. CuiG. FuX. WangW. ChenX. LiuS. CaoP. ZhaoS. LINC00476 Suppresses the Progression of Non-Small Cell Lung Cancer by Inducing the Ubiquitination of SETDB1.Radiat. Res.2020195327528310.1667/RADE‑20‑00105.133370431
     [Google Scholar]
  123. LiQ. LiY. WangY. CuiZ. GongL. QuZ. ZhongY. ZhouJ. ZhouY. GaoY. LiY. Quantitative proteomic study of human prostate cancer cells with different metastatic potentials.Int. J. Oncol.20164841437144610.3892/ijo.2016.337826846621
     [Google Scholar]
  124. LiW. YangX. LiuX. DengH. LiW. HeX. ZhangW. ShenY. LiX. PengQ. LiuD. SETDB1 confers colorectal cancer metastasis by regulation of WNT/β-catenin signaling.Biochim. Biophys. Acta, Gen. Subj.20231867713037710.1016/j.bbagen.2023.13037737169209
     [Google Scholar]
  125. KongJ. XuS. DengZ. WangY. ZhangP. Transcription factor FOXM1 promotes hepatocellular carcinoma malignant progression through activation of the WNT pathway by binding to SETDB1.Tissue Cell20238410218610.1016/j.tice.2023.10218637556918
     [Google Scholar]
  126. TakadaI. KouzmenkoA.P. KatoS. Wnt and PPARγ signaling in osteoblastogenesis and adipogenesis.Nat. Rev. Rheumatol.20095844244710.1038/nrrheum.2009.13719581903
     [Google Scholar]
  127. BeyerS. PontisJ. SchirwisE. BattistiV. RudolfA. Le GrandF. Ait-Si-AliS. Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation.Cell Discov.2016211603710.1038/celldisc.2016.3727790377
     [Google Scholar]
  128. LuqmaniY.A. Mechanisms of drug resistance in cancer chemotherapy.Med. Princ. Pract.200514Suppl. 1354810.1159/00008618316103712
     [Google Scholar]
  129. BarcelóF. ScottaC. Ortiz-LombardíaM. MéndezC. SalasJ.A. PortugalJ. Entropically-driven binding of mithramycin in the minor groove of C/G-rich DNA sequences.Nucleic Acids Res.20073572215222610.1093/nar/gkm03717369273
     [Google Scholar]
  130. SastryM. PatelD.J. Solution structure of the mithramycin dimer-DNA complex.Biochemistry199332266588660410.1021/bi00077a0128329387
     [Google Scholar]
  131. AlbertiniV. JainA. VignatiS. NapoliS. RinaldiA. KweeI. Nur-e-AlamM. BergantJ. BertoniF. CarboneG.M. RohrJ. CatapanoC.V. Novel GC-rich DNA-binding compound produced by a genetically engineered mutant of the mithramycin producer Streptomyces argillaceus exhibits improved transcriptional repressor activity: implications for cancer therapy.Nucleic Acids Res.20063461721173410.1093/nar/gkl06316571899
     [Google Scholar]
  132. SafeS. AbdelrahimM. Sp transcription factor family and its role in cancer.Eur. J. Cancer200541162438244810.1016/j.ejca.2005.08.00616209919
     [Google Scholar]
  133. AnJ. ZhangX. QinJ. WanY. HuY. LiuT. LiJ. DongW. DuE. PanC. ZengW. The histone methyltransferase ESET is required for the survival of spermatogonial stem/progenitor cells in mice.Cell Death Dis.201454e119610.1038/cddis.2014.17124763053
     [Google Scholar]
  134. PrevidiS. MalekA. AlbertiniV. RivaC. CapellaC. BrogginiM. CarboneG.M. RohrJ. CatapanoC.V. Inhibition of Sp1-dependent transcription and antitumor activity of the new aureolic acid analogues mithramycin SDK and SK in human ovarian cancer xenografts.Gynecol. Oncol.2010118218218810.1016/j.ygyno.2010.03.02020452660
     [Google Scholar]
  135. BlumeS.W. SnyderR.C. RayR. ThomasS. KollerC.A. MillerD.M. Mithramycin inhibits SP1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo.J. Clin. Invest.19918851613162110.1172/JCI1154741834700
     [Google Scholar]
  136. RemsingL.L. GonzálezA.M. Nur-e-AlamM. Fernández-LozanoM.J. BrañaA.F. RixU. OliveiraM.A. MéndezC. SalasJ.A. RohrJ. Mithramycin SK, a novel antitumor drug with improved therapeutic index, mithramycin SA, and demycarosyl-mithramycin SK: three new products generated in the mithramycin producer Streptomyces argillaceus through combinatorial biosynthesis.J. Am. Chem. Soc.2003125195745575310.1021/ja034162h12733914
     [Google Scholar]
  137. GibsonM. Nur-e-alamM. LipataF. OliveiraM.A. RohrJ. Characterization of kinetics and products of the Baeyer-Villiger oxygenase MtmOIV, the key enzyme of the biosynthetic pathway toward the natural product anticancer drug mithramycin from Streptomyces argillaceus.J. Am. Chem. Soc.200512750175941759510.1021/ja055750t16351075
     [Google Scholar]
  138. NohH.J. KimK.A. KimK.C. p53 Down-regulates SETDB1 gene expression during paclitaxel induced-cell death.Biochem. Biophys. Res. Commun.20144461434810.1016/j.bbrc.2014.02.05324565839
     [Google Scholar]
  139. MarkouliM. StrepkosD. ChlamydasS. PiperiC. Histone lysine methyltransferase SETDB1 as a novel target for central nervous system diseases.Prog. Neurobiol.202120010196810.1016/j.pneurobio.2020.10196833279625
     [Google Scholar]
  140. GhelaniH.S. RachchhM.A. GokaniR.H. MicroRNAs as newer therapeutic targets: A big hope from a tiny player.J. Pharmacol. Pharmacother.20123321722710.4103/0976‑500X.9941623129956
     [Google Scholar]
  141. CarthewR.W. SontheimerE.J. Origins and Mechanisms of miRNAs and siRNAs.Cell2009136464265510.1016/j.cell.2009.01.03519239886
     [Google Scholar]
  142. GambariR. BrognaraE. SpandidosD.A. FabbriE. Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review).Int. J. Oncol.201649153210.3892/ijo.2016.350327175518
     [Google Scholar]
  143. ChenB. WangJ. WangJ. WangH. GuX. TangL. FengX. A regulatory circuitry comprising TP53, miR-29 family, and SETDB1 in non-small cell lung cancer.Biosci. Rep.2018385BSR2018067810.1042/BSR2018067830054425
     [Google Scholar]
  144. ChenX. LiX. WeiC. ZhaoC. WangS. GaoJ. High expression of SETDB1 mediated by miR-29a-3p associates with poor prognosis and immune invasion in breast invasive carcinoma.Transl. Cancer Res.202110125065507510.21037/tcr‑21‑152735116358
     [Google Scholar]
  145. LiuS. LiB. XuJ. HuS. ZhanN. WangH. GaoC. LiJ. XuX. SOD1 Promotes Cell Proliferation and Metastasis in Non-small Cell Lung Cancer via an miR-409-3p/SOD1/SETDB1 Epigenetic Regulatory Feedforward Loop.Front. Cell Dev. Biol.2020821310.3389/fcell.2020.0021332391354
     [Google Scholar]
  146. WuM. FanB. GuoQ. LiY. ChenR. LvN. DiaoY. LuoY. Knockdown of SETDB1 inhibits breast cancer progression by miR-381-3p-related regulation.Biol. Res.20185113910.1186/s40659‑018‑0189‑030309377
     [Google Scholar]
  147. ShaoY. SongX. JiangW. ChenY. NingZ. GuW. JiangJ. MicroRNA-621 Acts as a Tumor Radiosensitizer by Directly Targeting SETDB1 in Hepatocellular Carcinoma.Mol. Ther.201927235536410.1016/j.ymthe.2018.11.00530503969
     [Google Scholar]
  148. SinghS.K. BahalR. RasmussenT.P. Evidence that miR-152-3p is a positive regulator of SETDB1-mediated H3K9 histone methylation and serves as a toggle between histone and DNA methylation.Exp. Cell Res.2020395211221610.1016/j.yexcr.2020.11221632768498
     [Google Scholar]
  149. TanJ. YangX. ZhuangL. JiangX. ChenW. LeeP.L. KaruturiR.K.M. TanP.B.O. LiuE.T. YuQ. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells.Genes Dev.20072191050106310.1101/gad.152410717437993
     [Google Scholar]
  150. CarvalhoS. FreitasM. AntunesL. Monteiro-ReisS. Vieira-CoimbraM. TavaresA. PaulinoS. VideiraJ.F. JerónimoC. HenriqueR. Prognostic value of histone marks H3K27me3 and H3K9me3 and modifying enzymes EZH2, SETDB1 and LSD-1 in colorectal cancer.J. Cancer Res. Clin. Oncol.2018144112127213710.1007/s00432‑018‑2733‑230105513
     [Google Scholar]
  151. JiangH. LiY. XiangX. TangZ. LiuK. SuQ. ZhangX. LiL. Chaetocin: A review of its anticancer potentials and mechanisms.Eur. J. Pharmacol.202191017445910.1016/j.ejphar.2021.17445934464601
     [Google Scholar]
  152. XinD.E. LiaoY. RaoR. OgurekS. SenguptaS. XinM. BayatA.E. SeibelW.L. GrahamR.T. KoschmannC. LuQ.R. Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201.Neuro-oncol.202426473574810.1093/neuonc/noad22238011799
     [Google Scholar]
  153. ChibaT. SaitoT. YukiK. ZenY. KoideS. KanogawaN. MotoyamaT. OgasawaraS. SuzukiE. OokaY. TawadaA. OtsukaM. MiyazakiM. IwamaA. YokosukaO. Histone lysine methyltransferase SUV39H1 is a potent target for epigenetic therapy of hepatocellular carcinoma.Int. J. Cancer2015136228929810.1002/ijc.2898524844570
     [Google Scholar]
  154. CherblancF.L. ChapmanK.L. ReidJ. BorgA.J. SundriyalS. Alcazar-FuoliL. BignellE. DemetriadesM. SchofieldC.J. DiMaggioP.A.Jr BrownR. FuchterM.J. On the histone lysine methyltransferase activity of fungal metabolite chaetocin.J. Med. Chem.201356218616862510.1021/jm401063r24099080
     [Google Scholar]
  155. GuoY. MaoX. XiongL. XiaA. YouJ. LinG. WuC. HuangL. WangY. YangS. Structure‐Guided Discovery of a Potent and Selective Cell‐Active Inhibitor of SETDB1 Tudor Domain.Angew. Chem. Int. Ed.202160168760876510.1002/anie.20201720033511756
     [Google Scholar]
  156. UguenM. DengY. LiF. ShellD.J. Norris-DrouinJ.L. StashkoM.A. AcklooS. ArrowsmithC.H. JamesL.I. LiuP. PearceK.H. FryeS.V. SETDB1 Triple Tudor Domain Ligand, ( R, R )-59, Promotes Methylation of Akt1 in Cells.ACS Chem. Biol.20231881846185310.1021/acschembio.3c0028037556795
     [Google Scholar]
  157. Casado-PelaezM. Bueno-CostaA. EstellerM. Single cell cancer epigenetics.Trends Cancer202281082083810.1016/j.trecan.2022.06.00535821003
     [Google Scholar]
  158. DavalosV. EstellerM. Cancer epigenetics in clinical practice.CA Cancer J. Clin.202373437642410.3322/caac.2176536512337
     [Google Scholar]
  159. TsaiH.C. BaylinS.B. Cancer epigenetics: linking basic biology to clinical medicine.Cell Res.201121350251710.1038/cr.2011.2421321605
     [Google Scholar]
  160. MannB.S. JohnsonJ.R. CohenM.H. JusticeR. PazdurR. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma.Oncologist200712101247125210.1634/theoncologist.12‑10‑124717962618
     [Google Scholar]
  161. LeeH.Z. KwitkowskiV.E. Del ValleP.L. RicciM.S. SaberH. HabtemariamB.A. BullockJ. BloomquistE. Li ShenY. ChenX.H. BrownJ. MehrotraN. DorffS. CharlabR. KaneR.C. KaminskasE. JusticeR. FarrellA.T. PazdurR. FDA Approval: Belinostat for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma.Clin. Cancer Res.201521122666267010.1158/1078‑0432.CCR‑14‑311925802282
     [Google Scholar]
  162. SchiffmanJ.D. FisherP.G. GibbsP. Early detection of cancer: past, present, and future.Am Soc Clin Oncol Educ Book.20152015576510.14694/EdBook_AM.2015.35.57
     [Google Scholar]
  163. SchwartzentruberJ. KorshunovA. LiuX.Y. JonesD.T.W. PfaffE. JacobK. SturmD. FontebassoA.M. QuangD.A.K. TönjesM. HovestadtV. AlbrechtS. KoolM. NantelA. KonermannC. LindrothA. JägerN. RauschT. RyzhovaM. KorbelJ.O. HielscherT. HauserP. GaramiM. KleknerA. BognarL. EbingerM. SchuhmannM.U. ScheurlenW. PekrunA. FrühwaldM.C. RoggendorfW. KrammC. DürkenM. AtkinsonJ. LepageP. MontpetitA. ZakrzewskaM. ZakrzewskiK. LiberskiP.P. DongZ. SiegelP. KulozikA.E. ZapatkaM. GuhaA. MalkinD. FelsbergJ. ReifenbergerG. von DeimlingA. IchimuraK. CollinsV.P. WittH. MildeT. WittO. ZhangC. Castelo-BrancoP. LichterP. FauryD. TaboriU. PlassC. MajewskiJ. PfisterS.M. JabadoN. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.Nature2012482738422623110.1038/nature1083322286061
     [Google Scholar]
  164. KarremannM. GielenG.H. HoffmannM. WieseM. ColditzN. Warmuth-MetzM. BisonB. ClaviezA. van VuurdenD.G. von BuerenA.O. GessiM. KühnleI. HansV.H. BeneschM. SturmD. KortmannR.D. WahaA. PietschT. KrammC.M. Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location.Neuro-oncol.201820112313110.1093/neuonc/nox14929016894
     [Google Scholar]
/content/journals/ccdt/10.2174/0115680096311909240721160523
Loading
Targeting the Tumor Epigenetic Regulator SETDB1 for Tumor Therapy
Curr. Cancer Drug Targets< 25, 945 (2025); https://doi.org/10.2174/0115680096311909240721160523
/content/journals/ccdt/10.2174/0115680096311909240721160523
/content/journals/ccdt/10.2174/0115680096311909240721160523
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): cancer progression; Epigenetic modification; histone methyltransferase SETDB1; inhibitor; signal pathways; tumor therapy

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test