Các methyltransferase trong bệnh sinh của các loại ung thư keratinocyte
Tóm tắt
Chứng cứ gần đây cho thấy rằng sự rối loạn biểu hiện gen do những thay đổi trong DNA, RNA và methyl hóa histone có thể là những yếu tố quan trọng góp phần vào bệnh sinh của các loại ung thư keratinocyte (KC), bao gồm ung thư biểu mô tế bào đáy (BCC) và ung thư biểu mô tế bào vảy da (cSCC), mà tổng số ca mắc của chúng vượt qua tất cả các loại ung thư khác ở người. Trong khi rõ ràng rằng các yếu tố điều biến methyl hóa thường bị rối loạn trong KC, những thay đổi phân tử và cơ chế cơ bản chỉ mới bắt đầu được hiểu rõ. Thú vị thay, gần đây đã xuất hiện bằng chứng cho thấy có sự tương tác sâu rộng giữa các quá trình methyl hóa khác nhau này. Ở đây, chúng tôi tóm tắt và tổng hợp những phát hiện mới nhất trong lĩnh vực này và làm nổi bật cách mà những khám phá này có thể mở ra những phương pháp điều trị mới cho những căn bệnh ung thư phổ biến này.
Từ khóa
Tài liệu tham khảo
Cavalli, 2019, Advances in epigenetics link genetics to the environment and disease, Nature, 571, 489, 10.1038/s41586-019-1411-0
Michalak, 2019, The roles of DNA, RNA and histone methylation in ageing and cancer, Nat. Rev. Mol. Cell Biol., 20, 573, 10.1038/s41580-019-0143-1
Singh, 2017, Towards therapeutic advances in melanoma management: An overview, Life Sci., 174, 50, 10.1016/j.lfs.2017.02.011
Penta, 2017, Epigenetics of skin cancer: Interventions by selected bioactive phytochemicals, Photodermatol. Photoimmunol. Photomed., 34, 42, 10.1111/phpp.12353
Ratushny, 2012, From keratinocyte to cancer: The pathogenesis and modeling of cutaneous squamous cell carcinoma, J. Clin. Investig., 122, 464, 10.1172/JCI57415
Nikolouzakis, T.K., Falzone, L., Lasithiotakis, K., Krüger-Krasagakis, S., Kalogeraki, A., Sifaki, M., Spandidos, D.A., Chrysos, E., Tsatsakis, A., and Tsiaoussis, J. (2020). Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer. J. Clin. Med., 9.
Sang, 2019, Current insights into the epigenetic mechanisms of skin cancer, Dermatol. Ther., 32, e12964, 10.1111/dth.12964
Que, 2018, Cutaneous squamous cell carcinoma, J. Am. Acad. Dermatol., 78, 237, 10.1016/j.jaad.2017.08.059
Maturo, 2020, Coding and noncoding somatic mutations in candidate genes in basal cell carcinoma, Sci. Rep., 10, 1, 10.1038/s41598-020-65057-2
Cerami, 2012, The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data, Cancer Discov., 2, 401, 10.1158/2159-8290.CD-12-0095
Gao, 2013, Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal, Sci. Signal., 6, pl1, 10.1126/scisignal.2004088
Tate, 2018, COSMIC: The Catalogue of Somatic Mutations in Cancer, Nucleic Acids Res., 47, D941, 10.1093/nar/gky1015
Li, 1998, Induction of Squamous Cell Carcinoma in p53-Deficient Mice after Ultraviolet Irradiation, J. Investig. Derm., 110, 72, 10.1046/j.1523-1747.1998.00090.x
Berg, 1996, Early p53 alterations in mouse skin carcinogenesis by UVB radiation: Immunohistochemical detection of mutant p53 protein in clusters of preneoplastic epidermal cells, Proc. Natl. Acad. Sci. USA, 93, 274, 10.1073/pnas.93.1.274
South, 2014, NOTCH1 Mutations Occur Early during Cutaneous Squamous Cell Carcinogenesis, J. Investig. Dermatol., 134, 2630, 10.1038/jid.2014.154
Fowler, 2021, Selection of Oncogenic Mutant Clones in Normal Human Skin Varies with Body Site, Cancer Discov., 11, 340, 10.1158/2159-8290.CD-20-1092
Yilmaz, 2017, Differential mutation frequencies in metastatic cutaneous squamous cell carcinomas versus primary tumors, Cancer, 123, 1184, 10.1002/cncr.30459
Pickering, 2014, Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma, Clin. Cancer Res., 20, 6582, 10.1158/1078-0432.CCR-14-1768
Kumar, 2018, Epigenetics of Modified DNA Bases: 5-Methylcytosine and Beyond, Front. Genet., 9, 640, 10.3389/fgene.2018.00640
Zhang, 2017, DNA methyltransferases and their roles in tumorigenesis, Biomark. Res., 5, 1, 10.1186/s40364-017-0081-z
Jeong, 2009, Selective Anchoring of DNA Methyltransferases 3A and 3B to Nucleosomes Containing Methylated DNA, Mol. Cell. Biol., 29, 5366, 10.1128/MCB.00484-09
Okano, 1999, DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development, Cell, 99, 247, 10.1016/S0092-8674(00)81656-6
Uysal, 2015, Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos, Biochimie, 116, 103, 10.1016/j.biochi.2015.06.019
Sen, 2010, DNMT1 maintains progenitor function in self-renewing somatic tissue, Nat. Cell Biol., 463, 563
Li, 2012, Progressive Alopecia Reveals Decreasing Stem Cell Activation Probability during Aging of Mice with Epidermal Deletion of DNA Methyltransferase 1, J. Investig. Dermatol., 132, 2681, 10.1038/jid.2012.206
Rinaldi, 2016, Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis, Cell Stem Cell, 19, 491, 10.1016/j.stem.2016.06.020
Rinaldi, 2017, Loss of Dnmt3a and Dnmt3b does not affect epidermal homeostasis but promotes squamous transformation through PPAR-γ, eLife, 6, e21697, 10.7554/eLife.21697
Guo, 2011, Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult Brain, Cell, 145, 423, 10.1016/j.cell.2011.03.022
He, 2011, Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA, Science, 333, 1303, 10.1126/science.1210944
An, 2017, TET family dioxygenases and DNA demethylation in stem cells and cancers, Exp. Mol. Med., 49, e323, 10.1038/emm.2017.5
Fritz, 2010, Cytidine deaminases: AIDing DNA demethylation?, Genes Dev., 24, 2107, 10.1101/gad.1963010
Kohli, 2013, TET enzymes, TDG and the dynamics of DNA demethylation, Nat. Cell Biol., 502, 472
Kunz, 2011, Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability, Nat. Cell Biol., 470, 419
Bormann, 2018, Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin, Nat. Commun., 9, 1
Hervás-Marín, D., Higgins, F., Sanmartín, O., López-Guerrero, J.A., Bañó, M.C., Igual, J.C., Quilis, I., and Sandoval, J. (2019). Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma. PLoS ONE, 14.
Li, 2020, UVB induces cutaneous squamous cell carcinoma progression by de novo ID4 methylation via methylation regulating enzymes, EBioMedicine, 57, 102835, 10.1016/j.ebiom.2020.102835
Liang, 2015, Secreted frizzled-related protein promotors are hypermethylated in cutaneous squamous carcinoma compared with normal epidermis, BMC Cancer, 15, 1, 10.1186/s12885-015-1650-x
Brown, 2004, p16INK4a and p14ARF Tumor Suppressor Genes Are Commonly Inactivated in Cutaneous Squamous Cell Carcinoma, J. Investig. Dermatol., 122, 1284, 10.1111/j.0022-202X.2004.22501.x
Chiles, 2003, E-Cadherin Promoter Hypermethylation in Preneoplastic and Neoplastic Skin Lesions, Mod. Pathol., 16, 1014, 10.1097/01.MP.0000089779.35435.9D
Murao, 2006, Epigenetic abnormalities in cutaneous squamous cell carcinomas: Frequent inactivation of the RB1/p16 and p53 pathways, Br. J. Dermatol., 155, 999, 10.1111/j.1365-2133.2006.07487.x
Takeuchi, 2002, Loss of T-Cadherin (CDH13, H-Cadherin) Expression in Cutaneous Squamous Cell Carcinoma, Lab. Investig., 82, 1023, 10.1097/01.LAB.0000025391.35798.F1
Venza, 2009, FOXE1 is a target for aberrant methylation in cutaneous squamous cell carcinoma, Br. J. Dermatol., 162, 1093, 10.1111/j.1365-2133.2009.09560.x
Meier, K., Drexler, S.K., Eberle, F.C., Lefort, K., and Yazdi, A.S. (2016). Silencing of ASC in Cutaneous Squamous Cell Carcinoma. PLoS ONE, 11.
Nobeyama, Y., Watanabe, Y., and Nakagawa, H. (2017). Silencing of G0/G1 switch gene 2 in cutaneous squamous cell carcinoma. PLoS ONE, 12.
Li, 2015, Aberrant Methylation Changes Detected in Cutaneous Squamous Cell Carcinoma of Immunocompetent Individuals, Cell Biophys., 72, 599, 10.1007/s12013-014-0507-2
Lang, C.M.R., Chan, C.K., Veltri, A., and Lien, W.-H. (2019). Wnt Signaling Pathways in Keratinocyte Carcinomas. Cancers, 11.
Darr, 2015, Epigenetic alterations in metastatic cutaneous carcinoma, Head Neck, 37, 994, 10.1002/hed.23701
Haider, 2006, Genomic Analysis Defines a Cancer-Specific Gene Expression Signature for Human Squamous Cell Carcinoma and Distinguishes Malignant Hyperproliferation from Benign Hyperplasia, J. Investig. Dermatol., 126, 869, 10.1038/sj.jid.5700157
Yooyongsatit, 2015, Patterns and functional roles of LINE-1 and Alu methylation in the keratinocyte from patients with psoriasis vulgaris, J. Hum. Genet., 60, 349, 10.1038/jhg.2015.33
Wei, 2003, Identification of Dss1 as a 12-O-Tetradecanoylphorbol-13-acetate-responsive Gene Expressed in Keratinocyte Progenitor Cells, with Possible Involvement in Early Skin Tumorigenesis, J. Biol. Chem., 278, 1758, 10.1074/jbc.M206328200
Venza, 2017, DSS1 promoter hypomethylation and overexpression predict poor prognosis in melanoma and squamous cell carcinoma patients, Hum. Pathol., 60, 137, 10.1016/j.humpath.2016.10.018
Brinkhuizen, T., Hurk, K.V.D., Winnepenninckx, V.J.L., De Hoon, J.P., Van Marion, A.M., Veeck, J., Van Engeland, M., and van Steensel, M. (2012). Epigenetic Changes in Basal Cell Carcinoma Affect SHH and WNT Signaling Components. PLoS ONE, 7.
Stamatelli, 2014, Epigenetic alterations in sporadic basal cell carcinomas, Arch. Dermatol. Res., 306, 561, 10.1007/s00403-014-1454-x
Cutter, 2015, A brief review of nucleosome structure, FEBS Lett., 589, 2914, 10.1016/j.febslet.2015.05.016
Boopathi, 2017, Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1, Mol. Cell, 66, 384, 10.1016/j.molcel.2017.04.012
Kalashnikova, 2016, Linker histone H1 and protein–protein interactions, Biochim. Biophys. Acta BBA Gene Regul. Mech., 1859, 455, 10.1016/j.bbagrm.2015.10.004
Black, 2012, Histone Lysine Methylation Dynamics: Establishment, Regulation, and Biological Impact, Mol. Cell, 48, 491, 10.1016/j.molcel.2012.11.006
Hyun, 2017, Writing, erasing and reading histone lysine methylations, Exp. Mol. Med., 49, e324, 10.1038/emm.2017.11
Weirich, 2015, Somatic cancer mutations in the MLL3-SET domain alter the catalytic properties of the enzyme, Clin. Epigenet., 7, 36, 10.1186/s13148-015-0075-3
Lee, 2008, Targeted inactivation of MLL3 histone H3-Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis, Proc. Natl. Acad. Sci. USA, 105, 19229, 10.1073/pnas.0810100105
Wu, 2013, Molecular Basis for the Regulation of the H3K4 Methyltransferase Activity of PRDM9, Cell Rep., 5, 13, 10.1016/j.celrep.2013.08.035
Fritsch, 2010, A Subset of the Histone H3 Lysine 9 Methyltransferases Suv39h1, G9a, GLP, and SETDB1 Participate in a Multimeric Complex, Mol. Cell, 37, 46, 10.1016/j.molcel.2009.12.017
Husmann, 2019, Histone lysine methyltransferases in biology and disease, Nat. Struct. Mol. Biol., 26, 880, 10.1038/s41594-019-0298-7
Godfrey, 2019, DOT1L inhibition reveals a distinct subset of enhancers dependent on H3K79 methylation, Nat. Commun., 10, 1, 10.1038/s41467-019-10844-3
Wu, 2013, Crystal structures of the human histone H4K20 methyltransferases SUV420H1 and SUV420H2, FEBS Lett., 587, 3859, 10.1016/j.febslet.2013.10.020
Yoo, 2012, EZH2 Methyltransferase and H3K27 Methylation in Breast Cancer, Int. J. Biol. Sci., 8, 59, 10.7150/ijbs.8.59
Li, 2015, Genomic Analysis of Metastatic Cutaneous Squamous Cell Carcinoma, Clin. Cancer Res., 21, 1447, 10.1158/1078-0432.CCR-14-1773
Martincorena, 2015, High burden and pervasive positive selection of somatic mutations in normal human skin, Science, 348, 880, 10.1126/science.aaa6806
Soares, 2017, Master regulatory role of p63 in epidermal development and disease, Cell. Mol. Life Sci., 75, 1179, 10.1007/s00018-017-2701-z
Shiao, 2018, KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis, Genes Dev., 32, 181, 10.1101/gad.306241.117
Egolf, S., Zou, J., Anderson, A., Aubert, Y., Ge, K., Seykora, J.T., and Capell, B.C. (2021). MLL4 Is a Critical Mediator of Differentiation and Ferroptosis in the Epidermis. bioRxiv.
Egolf, 2019, LSD1 Inhibition Promotes Epithelial Differentiation through Derepression of Fate-Determining Transcription Factors, Cell Rep., 28, 1981, 10.1016/j.celrep.2019.07.058
Yan, K.-S., Lin, C.-Y., Liao, T.-W., Peng, C.-M., Lee, S.-C., Liu, Y.-J., Chan, W.P., and Chou, R.-H. (2017). EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?. Int. J. Mol. Sci., 18.
Breuer, 2004, Increased Expression of the EZH2 Polycomb Group Gene in BMI-1-Positive Neoplastic Cells during Bronchial Carcinogenesis, Neoplasia, 6, 736, 10.1593/neo.04160
Simon, 2008, Roles of the EZH2 histone methyltransferase in cancer epigenetics, Mutat. Res. Mol. Mech. Mutagen., 647, 21, 10.1016/j.mrfmmm.2008.07.010
Yamagishi, 2017, Targeting EZH2 in cancer therapy, Curr. Opin. Oncol., 29, 375, 10.1097/CCO.0000000000000390
Zhao, 2014, Role of EZH2 in oral squamous cell carcinoma carcinogenesis, Gene, 537, 197, 10.1016/j.gene.2014.01.006
He, 2009, High expression of EZH2 is associated with tumor aggressiveness and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy, Int. J. Cancer, 127, 138, 10.1002/ijc.25031
Liu, 2015, Aberrant overexpression of EZH2 and H3K27me3 serves as poor prognostic biomarker for esophageal squamous cell carcinoma patients, Biomarkers, 21, 80, 10.3109/1354750X.2015.1118537
Kidani, 2009, High expression of EZH2 is associated with tumor proliferation and prognosis in human oral squamous cell carcinomas, Oral Oncol., 45, 39, 10.1016/j.oraloncology.2008.03.016
Cao, 2011, EZH2 Promotes Malignant Phenotypes and Is a Predictor of Oral Cancer Development in Patients with Oral Leukoplakia, Cancer Prev. Res., 4, 1816, 10.1158/1940-6207.CAPR-11-0130
Izzo, 1998, Dysregulated cyclin D1 expression early in head and neck tumorigenesis: In vivo evidence for an association with subsequent gene amplification, Oncogene, 17, 2313, 10.1038/sj.onc.1202153
Toll, 2018, The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma, Carcinogenesis, 39, 503, 10.1093/carcin/bgy016
Chen, 2020, Histone methyltransferase SETD2: A potential tumor suppressor in solid cancers, J. Cancer, 11, 3349, 10.7150/jca.38391
Fahey, 2017, SETting the Stage for Cancer Development: SETD2 and the Consequences of Lost Methylation, Cold Spring Harb. Perspect. Med., 7, a026468, 10.1101/cshperspect.a026468
Mar, 2017, SETD2 Alterations Impair DNA Damage Recognition and Lead to Resistance to Chemotherapy in Leuke-mia, Blood, 130, 2631, 10.1182/blood-2017-03-775569
Bhattacharya, 2021, The methyltransferase SETD2 couples transcription and splicing by engaging mRNA processing factors through its SHI domain, Nat. Commun., 12, 1, 10.1038/s41467-021-21663-w
Seervai, 2020, The Huntingtin-interacting protein SETD2/HYPB is an actin lysine methyltransferase, Sci. Adv., 6, eabb7854, 10.1126/sciadv.abb7854
Park, 2016, Dual Chromatin and Cytoskeletal Remodeling by SETD2, Cell, 166, 950, 10.1016/j.cell.2016.07.005
Xie, 2008, Histone methyltransferase protein SETD2 interacts with p53 and selectively regulates its downstream genes, Cell. Signal., 20, 1671, 10.1016/j.cellsig.2008.05.012
Rao, 2016, EZH2, Proliferation Rate, and Aggressive Tumor Subtypes in Cutaneous Basal Cell Carcinoma, JAMA Oncol., 2, 962, 10.1001/jamaoncol.2016.0021
Rao, 2018, Epigenetic markers in basal cell carcinoma: Universal themes in oncogenesis and tumor stratification? A short report, Cell. Oncol., 41, 693, 10.1007/s13402-018-0402-8
Zaccara, 2019, Reading, writing and erasing mRNA methylation, Nat. Rev. Mol. Cell Biol., 20, 608, 10.1038/s41580-019-0168-5
Roundtree, 2017, Dynamic RNA Modifications in Gene Expression Regulation, Cell, 169, 1187, 10.1016/j.cell.2017.05.045
Wei, 2021, Chromatin and transcriptional regulation by reversible RNA methylation, Curr. Opin. Cell Biol., 70, 109, 10.1016/j.ceb.2020.11.005
Tzelepis, 2019, RNA-modifying enzymes and their function in a chromatin context, Nat. Struct. Mol. Biol., 26, 858, 10.1038/s41594-019-0312-0
Huang, 2019, Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally, Nat. Cell Biol., 567, 414
Liu, 2020, N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription, Science, 367, 580, 10.1126/science.aay6018
Xiang, 2017, RNA m6A methylation regulates the ultraviolet-induced DNA damage response, Nat. Cell Biol., 543, 573
Zhou, 2019, METTL3 mediated m6A modification plays an oncogenic role in cutaneous squamous cell carcinoma by regulating ΔNp63, Biochem. Biophys. Res. Commun., 515, 310, 10.1016/j.bbrc.2019.05.155
Xi, L., Carroll, T., Matos, I., Luo, J.-D., Polak, L., Pasolli, H.A., Jaffrey, S.R., and Fuchs, E. (2020). m6A RNA methylation impacts fate choices during skin morphogenesis. eLife, 9.
Lee, 2021, N 6-methyladenosine modification of lncRNA Pvt1 governs epidermal stemness, EMBO J., 40, e106276, 10.15252/embj.2020106276
Zhao, 2020, METTL3 Facilitates Oral Squamous Cell Carcinoma Tumorigenesis by Enhancing c-Myc Stability via YTHDF1-Mediated m6A Modification, Mol. Ther. Nucleic Acids, 20, 1, 10.1016/j.omtn.2020.01.033