Epigenetics and cutaneous neoplasms: from mechanism to therapy

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J. Clin. 60(5), 277–300 (2010).
  MedlineGoogle Scholar
• 2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J. Clin. 68(1), 7–30 (2018).
  MedlineGoogle Scholar
• 3. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012. JAMA Dermatol. 151(10), 1081–1086 (2015).
  MedlineGoogle Scholar
• 4. Health UDO, Services H. The surgeon general's call to action to prevent skin cancer (2014). https://pubmed.ncbi.nlm.nih.gov/25320835/
  Google Scholar
• 5. Korgavkar K, Xiong M, Weinstock M. Changing incidence trends of cutaneous T-cell lymphoma. JAMA Dermatol. 149(11), 1295–1299 (2013).
  MedlineGoogle Scholar
• 6. Zackheim HS, Amin S, Kashani-Sabet M, McMillan A. Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489 patients. J. Am. Acad. Dermatol. 40(3), 418–425 (1999).
  Medline CASGoogle Scholar
• 7. Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat. Med. 17(3), 330–339 (2011).
  Medline CASGoogle Scholar
• 8. Baylin SB, Herman JG. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet. 16(4), 168–174 (2000).
  Medline CASGoogle Scholar
• 9. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat. Rev. Cancer 4(2), 143–153 (2004).
  Medline CASGoogle Scholar
• 10. Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics 1(2), 239–259 (2009).
  CASGoogle Scholar
• 11. Iżykowska K. Methylation patterns of cutaneous T-cell lymphomas. Exp. Dermatol. 30(8), 1135–1140 (2021).
  Medline CASGoogle Scholar
• 12. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat. Rev. Drug Discov. 11(5), 384–400 (2012).
  Medline CASGoogle Scholar
• 13. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5(9), 769–784 (2006).
  Medline CASGoogle Scholar
• 14. Di Leva G, Croce CM. miRNA profiling of cancer. Curr. Opin. Genet. Dev. 23(1), 3–11 (2013).
  MedlineGoogle Scholar
• 15. Tong AW, Nemunaitis J. Modulation of miRNA activity in human cancer: a new paradigm for cancer gene therapy? Cancer Gene Ther. 15(6), 341–355 (2008).
  Medline CASGoogle Scholar
• 16. Yan H, Bu P. Non-coding RNA in cancer. Essays Biochem. 65(4), 625–639 (2021).
  Medline CASGoogle Scholar
• 17. Hu W, Fang L, Ni R, Zhang H, Pan G. Changing trends in the disease burden of non-melanoma skin cancer globally from 1990 to 2019 and its predicted level in 25 years. BMC Cancer 22(1), 836 (2022).
  Medline CASGoogle Scholar
• 18. Lukowiak TM, Aizman L, Perz A et al. Association of age, sex, race, and geographic region with variation of the ratio of basal cell to cutaneous squamous cell carcinomas in the United States. JAMA Dermatol. 156(11), 1192–1198 (2020).
  MedlineGoogle Scholar
• 19. Ciążyńska M, Kamińska-Winciorek G, Lange D et al. The incidence and clinical analysis of non-melanoma skin cancer. Sci. Rep. 11(1), 4337 (2021).
  Medline CASGoogle Scholar
• 20. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N. Engl. J. Med. 344(13), 975–983 (2001).
  Medline CASGoogle Scholar
• 21. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging. J. Am. Acad. Dermatol. 78(2), 237–247 (2018).
  MedlineGoogle Scholar
• 22. Martinez JC, Otley CC, Stasko T et al. Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study. Arch. Dermatol. 139(3), 301–306 (2003).
  MedlineGoogle Scholar
• 23. McLaughlin EJ, Miller L, Shin TM et al. Rate of regional nodal metastases of cutaneous squamous cell carcinoma in the immunosuppressed patient. Am. J. Otolaryngol. 38(3), 325–328 (2017).
  MedlineGoogle Scholar
• 24. Dotto GP, Rustgi AK. Squamous cell cancers: a unified perspective on biology and genetics. Cancer Cell 29(5), 622–637 (2016).
  Medline CASGoogle Scholar
• 25. Chen Y, Yi X, Sun N, Guo W, Li C. Epigenetics regulates antitumor immunity in melanoma. Front. Immunol. 13, 868786 (2022). •• Provides an in-depth overview of aberrant epigenetic modifications present in melanoma with a strong focus on immunology and immunotherapies.
  Medline CASGoogle Scholar
• 26. Murao K, Kubo Y, Ohtani N, Hara E, Arase S. Epigenetic abnormalities in cutaneous squamous cell carcinomas: frequent inactivation of the RB1/p16 and p53 pathways. Br. J. Dermatol. 155(5), 999–1005 (2006).
  Medline CASGoogle Scholar
• 27. Solé-Boldo L, Raddatz G, Gutekunst J et al. Differentiation-related epigenomic changes define clinically distinct keratinocyte cancer subclasses. Mol. Syst. Biol. 18(9), e11073 (2022).
  Medline CASGoogle Scholar
• 28. Kashyap MP, Sinha R, Mukhtar MS, Athar M. Epigenetic regulation in the pathogenesis of non-melanoma skin cancer. Semin. Cancer Biol. 83, 36–56 (2022). •• A recent review article that focuses on epigenetic dysregulation in nonmelanoma skin cancer. This article is a good resource for a deep-dive into epigenetic regulation of basal cell carcinoma.
  Medline CASGoogle Scholar
• 29. Tamas T, Baciut M, Nutu A et al. Is miRNA regulation the key to controlling non-melanoma skin cancer evolution? Genes (Basel) 12(12), 1929 (2021).
  Medline CASGoogle Scholar
• 30. Chen IP, Bender M, Spassova I et al. UV-type specific alteration of miRNA expression and its association with tumor progression and metastasis in SCC cell lines. J. Cancer Res. Clin. Oncol. 146(12), 3215–3231 (2020).
  Medline CASGoogle Scholar
• 31. Saha K, Hornyak TJ, Eckert RL. Epigenetic cancer prevention mechanisms in skin cancer. AAPS J. 15(4), 1064–1071 (2013).
  Medline CASGoogle Scholar
• 32. McDaniel B, Badri T, Steele RB. Basal cell carcinoma. In: StatPearls. StatPearls Publishing, FL, USA (2022).
  Google Scholar
• 33. Rao RC, Chan MP, Andrews CA, Kahana A. EZH2, proliferation rate, and aggressive tumor subtypes in cutaneous basal cell carcinoma. JAMA Oncol. 2(7), 962–963 (2016).
  MedlineGoogle Scholar
• 34. Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat. Rev. Cancer 8(10), 743–754 (2008).
  Medline CASGoogle Scholar
• 35. Krišto M, Šitum M, Čeović R. Systemic therapies for advanced basal cell and cutaneous squamous cell carcinomas: novel targeted therapies and immunotherapies. Acta Dermatovenerol. Croat. 28(2), 80–92 (2020).
  Medline CASGoogle Scholar
• 36. Sekulic A, Von Hoff D. Hedgehog pathway inhibition. Cell 164(5), 831 (2016).
  Medline CASGoogle Scholar
• 37. Rao RC, Chan MP, Andrews CA, Kahana A. Epigenetic markers in basal cell carcinoma: universal themes in oncogenesis and tumor stratification? A short report. Cell. Oncol. (Dordr.) 41(6), 693–698 (2018).
  Medline CASGoogle Scholar
• 38. Stamatelli A, Vlachou C, Aroni K, Papassideri I, Patsouris E, Saetta AA. Epigenetic alterations in sporadic basal cell carcinomas. Arch. Dermatol. Res. 306(6), 561–569 (2014).
  Medline CASGoogle Scholar
• 39. Brinkhuizen T, Van Den Hurk K, Winnepenninckx VJ et al. Epigenetic changes in basal cell carcinoma affect SHH and WNT signaling components. PLOS ONE 7(12), e51710 (2012).
  Medline CASGoogle Scholar
• 40. Lodygin D, Yazdi AS, Sander CA, Herzinger T, Hermeking H. Analysis of 14-3-3σ expression in hyperproliferative skin diseases reveals selective loss associated with CpG-methylation in basal cell carcinoma. Oncogene 22(35), 5519–5524 (2003).
  Medline CASGoogle Scholar
• 41. Goldberg M, Rummelt C, Laerm A, Helmbold P, Holbach LM, Ballhausen WG. Epigenetic silencing contributes to frequent loss of the fragile histidine triad tumour suppressor in basal cell carcinomas. Br. J. Dermatol. 155(6), 1154–1158 (2006).
  Medline CASGoogle Scholar
• 42. Al-Eryani L, Jenkins SF, States VA et al. miRNA expression profiles of premalignant and malignant arsenic-induced skin lesions. PLOS ONE 13(8), e0202579 (2018).
  MedlineGoogle Scholar
• 43. Aoki K, Taketo MM. Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J. Cell Sci. 120(Pt 19), 3327–3335 (2007).
  Medline CASGoogle Scholar
• 44. Van Doorn R, Zoutman WH, Dijkman R et al. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. J. Clin. Oncol. 23(17), 3886–3896 (2005).
  Medline CASGoogle Scholar
• 45. Baliñas-Gavira C, Rodríguez MI, Andrades A et al. Frequent mutations in the amino-terminal domain of BCL7A impair its tumor suppressor role in DLBCL. Leukemia 34(10), 2722–2735 (2020).
  Medline CASGoogle Scholar
• 46. Hajra KM, Fearon ER. Cadherin and catenin alterations in human cancer. Genes Chromosomes Cancer 34(3), 255–268 (2002).
  Medline CASGoogle Scholar
• 47. Li L, Jiang M, Feng Q et al. Aberrant methylation changes detected in cutaneous squamous cell carcinoma of immunocompetent individuals. Cell Biochem. Biophys. 72(2), 599–604 (2015).
  Medline CASGoogle Scholar
• 48. Andreeva AV, Kutuzov MA. Cadherin 13 in cancer. Genes Chromosomes Cancer 49(9), 775–790 (2010).
  Medline CASGoogle Scholar
• 49. Brown VL, Harwood CA, Crook T, Cronin JG, Kelsell DP, Proby CM. p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma. J. Invest. Dermatol. 122(5), 1284–1292 (2004).
  Medline CASGoogle Scholar
• 50. Wu J, Zhang JR, Qin J. Clinical significance of methylation of E-cadherin and p14ARF gene promoters in skin squamous cell carcinoma tissues. Int. J. Clin. Exp. Med. 7(7), 1808–1812 (2014).
  MedlineGoogle Scholar
• 51. Xia Y, Liu Y, Yang C et al. Dominant role of CDKN2B/p15INK4B of 9p21.3 tumor suppressor hub in inhibition of cell-cycle and glycolysis. Nat. Commun. 12(1), 2047 (2021).
  Medline CASGoogle Scholar
• 52. Yu X, Minter-Dykhouse K, Malureanu L et al. Chfr is required for tumor suppression and Aurora A regulation. Nat. Genet. 37(4), 401–406 (2005).
  Medline CASGoogle Scholar
• 53. Singh P, Ravanan P, Talwar P. Death associated protein kinase 1 (DAPK1): a regulator of apoptosis and autophagy. Front. Mol. Neurosci. 9, 46 (2016).
  MedlineGoogle Scholar
• 54. Waters CE, Saldivar JC, Hosseini SA, Huebner K. The FHIT gene product: tumor suppressor and genome “caretaker.” Cell. Mol. Life Sci. 71(23), 4577–4587 (2014).
  Medline CASGoogle Scholar
• 55. Venza I, Visalli M, Tripodo B et al. FOXE1 is a target for aberrant methylation in cutaneous squamous cell carcinoma. Br. J. Dermatol. 162(5), 1093–1097 (2010).
  Medline CASGoogle Scholar
• 56. Dai W, Meng X, Mo S et al. FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer. CCS 18(1), 7 (2020).
  Medline CASGoogle Scholar
• 57. Nobeyama Y, Watanabe Y, Nakagawa H. Silencing of G0/G1 switch gene 2 in cutaneous squamous cell carcinoma. PLOS ONE 12(10), e0187047 (2017).
  MedlineGoogle Scholar
• 58. Yim CY, Sekula DJ, Hever-Jardine MP et al. G0S2 suppresses oncogenic transformation by repressing a MYC-regulated transcriptional program. Cancer Res. 76(5), 1204–1213 (2016).
  Medline CASGoogle Scholar
• 59. Lai P, Wang Y. Epigenetics of cutaneous T-cell lymphoma: biomarkers and therapeutic potentials. Cancer Biol. Med. 18(1), 34–51 (2021).
  Medline CASGoogle Scholar
• 60. Yanamadala S, Ljungman M. Potential role of MLH1 in the induction of p53 and apoptosis by blocking transcription on damaged DNA templates. Mol. Cancer Res. 1(10), 747–754 (2003).
  Medline CASGoogle Scholar
• 61. Jones CL, Ferreira S, McKenzie RC et al. Regulation of T-plastin expression by promoter hypomethylation in primary cutaneous T-cell lymphoma. J. Invest. Dermatol. 132(8), 2042–2049 (2012).
  Medline CASGoogle Scholar
• 62. Velthaus A, Cornils K, Hennigs JK et al. The actin binding protein plastin-3 is involved in the pathogenesis of acute myeloid leukemia. Cancers 11(11), 1663 (2019).
  Medline CASGoogle Scholar
• 63. Boni C, Sorio C. The role of the tumor suppressor gene protein tyrosine phosphatase gamma in cancer. Front. Cell Dev. Biol. 9, 768969 (2021).
  MedlineGoogle Scholar
• 64. Meier K, Drexler SK, Eberle FC, Lefort K, Yazdi AS. Silencing of ASC in cutaneous squamous cell carcinoma. PLOS ONE 11(10), e0164742 (2016).
  MedlineGoogle Scholar
• 65. Ohtsuka T, Ryu H, Minamishima YA et al. ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway. Nat. Cell Biol. 6(2), 121–128 (2004).
  Medline CASGoogle Scholar
• 66. Amin KS, Banerjee PP. The cellular functions of RASSF1A and its inactivation in prostate cancer. J. Carcinog. 11, 3 (2012).
  MedlineGoogle Scholar
• 67. Wang Y, Gu X, Zhang G et al. SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+ lymphoproliferative disease by repressing p21. Blood 123(22), 3452–3461 (2014).
  Medline CASGoogle Scholar
• 68. Sun J, Yi S, Qiu L et al. SATB1 defines a subtype of cutaneous CD30+ lymphoproliferative disorders associated with a T-helper 17 cytokine profile. J. Invest. Dermatol. 138(8), 1795–1804 (2018).
  Medline CASGoogle Scholar
• 69. Poglio S, Merlio JP. SATB1 is a pivotal epigenetic biomarker in cutaneous T-cell lymphomas. J. Invest. Dermatol. 138(8), 1694–1696 (2018).
  Medline CASGoogle Scholar
• 70. Jeng KS, Chang CF, Lin SS. Sonic hedgehog signaling in organogenesis, tumors, and tumor microenvironments. Int. J. Mol. Sci. 21(3), 758 (2020).
  Medline CASGoogle Scholar
• 71. Yang HY, Wen YY, Chen CH, Lozano G, Lee MH. 14-3-3 sigma positively regulates p53 and suppresses tumor growth. Mol. Cell. Biol. 23(20), 7096–7107 (2003).
  Medline CASGoogle Scholar
• 72. Liang J, Kang X, Halifu Y et al. Secreted frizzled-related protein promotors are hypermethylated in cutaneous squamous carcinoma compared with normal epidermis. BMC Cancer 15, 641 (2015).
  MedlineGoogle Scholar
• 73. Darr OA, Colacino JA, Tang AL et al. Epigenetic alterations in metastatic cutaneous carcinoma. Head Neck 37(7), 994–1001 (2015).
  MedlineGoogle Scholar
• 74. Liang J, Kang X, Halifu Y et al. Secreted frizzled-related protein promotors are hypermethylated in cutaneous squamous carcinoma compared with normal epidermis. BMC Cancer 15(1), 641 (2015).
  MedlineGoogle Scholar
• 75. Greco SA, Chia J, Inglis KJ et al. Thrombospondin-4 is a putative tumour-suppressor gene in colorectal cancer that exhibits age-related methylation. BMC Cancer 10(1), 494 (2010).
  MedlineGoogle Scholar
• 76. O'Leary L, Van Der Sloot AM, Reis CR et al. Decoy receptors block TRAIL sensitivity at a supracellular level: the role of stromal cells in controlling tumour TRAIL sensitivity. Oncogene 35(10), 1261–1270 (2016).
  MedlineGoogle Scholar
• 77. Yoon MK, Ha JH, Lee MS, Chi SW. Structure and apoptotic function of p73. BMB Rep. 48(2), 81–90 (2015).
  Medline CASGoogle Scholar
• 78. Wei HP, Zhan S, Zhu QA et al. Genome-wide expression difference of microRNAs in basal cell carcinoma. J. Immunol. Res. 2021, 7223500 (2021).
  MedlineGoogle Scholar
• 79. Hu P, Ma L, Wu Z, Zheng G, Li J. Expression of miR-34a in basal cell carcinoma patients and its relationship with prognosis. J. BUON 24(3), 1283–1288 (2019).
  MedlineGoogle Scholar
• 80. Sand M, Bechara FG, Sand D et al. Long-noncoding RNAs in basal cell carcinoma. Tumour Biol. 37(8), 10595–10608 (2016).
  Medline CASGoogle Scholar
• 81. Sand M, Bechara FG, Sand D et al. Circular RNA expression in basal cell carcinoma. Epigenomics 8(5), 619–632 (2016).
  CASGoogle Scholar
• 82. Li Y, Li Y, Li L. Circular RNA hsa_Circ_0005795 mediates cell proliferation of cutaneous basal cell carcinoma via sponging miR-1231. Arch. Dermatol. Res. 313(9), 773–782 (2021).
  Medline CASGoogle Scholar
• 83. Dhanyamraju PK, Holz PS, Finkernagel F, Fendrich V, Lauth M. Histone deacetylase 6 represents a novel drug target in the oncogenic hedgehog signaling pathway. Mol. Cancer Ther. 14(3), 727–739 (2015).
  Medline CASGoogle Scholar
• 84. Coni S, Mancuso AB, Di Magno L et al. Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH medulloblastoma. Sci. Rep. 7, 44079 (2017).
  MedlineGoogle Scholar
• 85. Gruber W, Peer E, Elmer DP et al. Targeting class I histone deacetylases by the novel small molecule inhibitor 4SC-202 blocks oncogenic hedgehog-GLI signaling and overcomes smoothened inhibitor resistance. Int. J. Cancer 142(5), 968–975 (2018).
  Medline CASGoogle Scholar
• 86. Mirza AN, Fry MA, Urman NM et al. Combined inhibition of atypical PKC and histone deacetylase 1 is cooperative in basal cell carcinoma treatment. JCI Insight 2(21), e97071 (2017).
  MedlineGoogle Scholar
• 87. Zhao J, Quan H, Xie C, Lou L. NL-103, a novel dual-targeted inhibitor of histone deacetylases and hedgehog pathway, effectively overcomes vismodegib resistance conferred by Smo mutations. Pharmacol. Res. Perspect. 2(3), e00043 (2014).
  MedlineGoogle Scholar
• 88. Li J, Cai H, Li H et al. Combined inhibition of sonic hedgehog signaling and histone deacetylase is an effective treatment for liver cancer. Oncol. Rep. 41(3), 1991–1997 (2019).
  Medline CASGoogle Scholar
• 89. Kilgour JM, Shah A, Urman NM et al. Phase II open-label, single-arm trial to investigate the efficacy and safety of topical remetinostat gel in patients with basal cell carcinoma. Clin. Cancer Res. 27(17), 4717–4725 (2021).
  Medline CASGoogle Scholar
• 90. Chong CY, Goh MS, Porceddu SV, Rischin D, Lim AM. The current treatment landscape of cutaneous squamous cell carcinoma. Am. J. Clin. Dermatol. doi:10.1007/s40257-022-00742-8 (2022). (Epub ahead of print).
  MedlineGoogle Scholar
• 91. Hedberg ML, Berry CT, Moshiri AS et al. Molecular mechanisms of cutaneous squamous cell carcinoma. Int. J. Mol. Sci. 23(7), 3478 (2022).
  Medline CASGoogle Scholar
• 92. Inman GJ, Wang J, Nagano A et al. The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature. Nat. Commun. 9(1), 3667 (2018).
  MedlineGoogle Scholar
• 93. Grönniger E, Weber B, Heil O et al. Aging and chronic sun exposure cause distinct epigenetic changes in human skin. PLoS Genet. 6(5), e1000971 (2010).
  MedlineGoogle Scholar
• 94. Vandiver AR, Irizarry RA, Hansen KD et al. Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin. Genome Biol. 16(1), 80 (2015).
  MedlineGoogle Scholar
• 95. Boudra R, Woappi Y, Wang D et al. Regulation of 5-hydroxymethylcytosine by TET2 contributes to squamous cell carcinoma tumorigenesis. J. Invest. Dermatol. 142(5), 1270–1279.e1272 (2022).
  Medline CASGoogle Scholar
• 96. Hervas-Marin D, Higgins F, Sanmartin O et al. Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma. PLOS ONE 14(12), e0223341 (2019).
  Medline CASGoogle Scholar
• 97. Sand M, Hessam S, Amur S et al. Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma. J. Dermatol. Sci. 86(2), 142–148 (2017).
  Medline CASGoogle Scholar
• 98. Toll A, Salgado R, Espinet B et al. miR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression. Mol. Cancer 15(1), 53 (2016).
  MedlineGoogle Scholar
• 99. Das Mahapatra K, Pasquali L, Søndergaard JN et al. A comprehensive analysis of coding and non-coding transcriptomic changes in cutaneous squamous cell carcinoma. Sci. Rep. 10(1), 3637 (2020). •• A large sequencing study conducted to identify changes in coding and noncoding expression patterns across cutaneous squamous cell carcinoma (cSCC) samples. This is a great resource to better understand not only what coding genes could be driving cSCC but also the impact of noncoding mechanisms in cSCC-specific gene regulation.
  MedlineGoogle Scholar
• 100. Anastasi S, Alemà S, Segatto O. Making sense of Cbp/p300 loss of function mutations in skin tumorigenesis. J. Pathol. 250(1), 3–6 (2020).
  Medline CASGoogle Scholar
• 101. Zhang L, Shan X, Chen Q et al. Downregulation of HDAC3 by ginsenoside Rg3 inhibits epithelial–mesenchymal transition of cutaneous squamous cell carcinoma through c-Jun acetylation. J. Cell. Physiol. 234(12), 22207–22219 (2019).
  Medline CASGoogle Scholar
• 102. Hernández-Ruiz E, Toll A, García-Diez I et al. The polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma. Carcinogenesis 39(3), 503–513 (2018).
  Medline CASGoogle Scholar
• 103. Shea LK, Akhave NS, Sutton LA et al. Combined Kdm6a and Trp53 deficiency drives the development of squamous cell skin cancer in mice. J. Invest. Dermatol. doi:10.1016/j.jid.2022.08.037 (2022). (Epub ahead of print).
  MedlineGoogle Scholar
• 104. Dauch C, Shim S, Cole MW et al. KMT2D loss drives aggressive tumor phenotypes in cutaneous squamous cell carcinoma. Am. J. Cancer Res. 12(3), 1309–1322 (2022).
  Medline CASGoogle Scholar
• 105. Egolf S, Zou J, Anderson A et al. MLL4 mediates differentiation and tumor suppression through ferroptosis. Sci. Adv. 7(50), eabj9141 (2021).
  Medline CASGoogle Scholar
• 106. Egolf S, Aubert Y, Doepner M et al. LSD1 inhibition promotes epithelial differentiation through derepression of fate-determining transcription factors. Cell Rep. 28(8), 1981–1992.e1987 (2019).
  Medline CASGoogle Scholar
• 107. Zhou R, Gao Y, Lv D, Wang C, Wang D, Li Q. METTL3 mediated m6A modification plays an oncogenic role in cutaneous squamous cell carcinoma by regulating ΔNp63. Biochem. Biophys. Res. Commun. 515(2), 310–317 (2019).
  Medline CASGoogle Scholar
• 108. Kang T, Zhang C, Lei H et al. NPTX2 promotes epithelial–mesenchymal transition in cutaneous squamous cell carcinoma through METTL3-mediated N6-methyladenosine methylation of SNAIL. J. Invest. Dermatol. doi: 10.1016/j.jid.2022.12.015 (2023). (Epub ahead of print).
  Google Scholar
• 109. Willemze R, Cerroni L, Kempf W et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood 133(16), 1703–1714 (2019).
  Medline CASGoogle Scholar
• 110. Agar NS, Wedgeworth E, Crichton S et al. Survival outcomes and prognostic factors in mycosis fungoides/Sezary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J. Clin. Oncol. 28(31), 4730–4739 (2010).
  MedlineGoogle Scholar
• 111. Yumeen S, Girardi M. Insights into the molecular and cellular underpinnings of cutaneous T cell lymphoma. Yale J. Biol. Med. 93(1), 111–121 (2020). • Summarizes the current state of understanding about cutaneous T-cell lymphoma, a rarer malignancy, and the etiology that underlies disease development and progression.
  Medline CASGoogle Scholar
• 112. Duvic M, Talpur R, Ni X et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 109(1), 31–39 (2007).
  Medline CASGoogle Scholar
• 113. Olsen EA, Kim YH, Kuzel TM et al. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J. Clin. Oncol. 25(21), 3109–3115 (2007).
  Medline CASGoogle Scholar
• 114. Duvic M, Olsen EA, Breneman D et al. Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma. Clin. Lymphoma Myeloma 9(6), 412–416 (2009).
  MedlineGoogle Scholar
• 115. Prince HM, Dickinson M, Khot A. Romidepsin for cutaneous T-cell lymphoma. Future Oncol. 9(12), 1819–1827 (2013).
  CASGoogle Scholar
• 116. Vandermolen KM, McCulloch W, Pearce CJ, Oberlies NH. Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J. Antibiot. (Tokyo) 64(8), 525–531 (2011).
  Medline CASGoogle Scholar
• 117. Piekarz RL, Frye R, Turner M et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J. Clin. Oncol. 27(32), 5410–5417 (2009).
  Medline CASGoogle Scholar
• 118. Whittaker SJ, Demierre MF, Kim EJ et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J. Clin. Oncol. 28(29), 4485–4491 (2010).
  Medline CASGoogle Scholar
• 119. Moskowitz AJ, Horwitz SM. Targeting histone deacetylases in T-cell lymphoma. Leuk. Lymphoma 58(6), 1306–1319 (2017).
  Medline CASGoogle Scholar
• 120. O'Connor OA, Heaney ML, Schwartz L et al. Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies. J. Clin. Oncol. 24(1), 166–173 (2006).
  MedlineGoogle Scholar
• 121. Piekarz RL, Robey R, Sandor V et al. Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. Blood 98(9), 2865–2868 (2001).
  Medline CASGoogle Scholar
• 122. Valdez BC, Brammer JE, Li Y et al. Romidepsin targets multiple survival signaling pathways in malignant T cells. Blood Cancer J. 5, e357 (2015).
  Medline CASGoogle Scholar
• 123. Piekarz RL, Robey RW, Zhan Z et al. T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance. Blood 103(12), 4636–4643 (2004).
  Medline CASGoogle Scholar
• 124. Zhang C, Richon V, Ni X, Talpur R, Duvic M. Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. J. Invest. Dermatol. 125(5), 1045–1052 (2005).
  Medline CASGoogle Scholar
• 125. Conti C, Leo E, Eichler GS et al. Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage. Cancer Res. 70(11), 4470–4480 (2010).
  Medline CASGoogle Scholar
• 126. Rozati S, Cheng PF, Widmer DS, Fujii K, Levesque MP, Dummer R. Romidepsin and azacitidine synergize in their epigenetic modulatory effects to induce apoptosis in CTCL. Clin. Cancer Res. 22(8), 2020–2031 (2016).
  Medline CASGoogle Scholar
• 127. Marquard L, Gjerdrum LM, Christensen IJ, Jensen PB, Sehested M, Ralfkiaer E. Prognostic significance of the therapeutic targets histone deacetylase 1, 2, 6 and acetylated histone H4 in cutaneous T-cell lymphoma. Histopathology 53(3), 267–277 (2008).
  Medline CASGoogle Scholar
• 128. Qu K, Zaba LC, Satpathy AT et al. Chromatin accessibility landscape of cutaneous T cell lymphoma and dynamic response to HDAC inhibitors. Cancer Cell 32(1), 27–41 e24 (2017).
  Medline CASGoogle Scholar
• 129. McGirt LY, Jia P, Baerenwald DA et al. Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides. Blood 126(4), 508–519 (2015).
  Medline CASGoogle Scholar
• 130. Zhang P, Zhang M. Epigenetics in the pathogenesis and treatment of cutaneous T-cell lymphoma. Front. Oncol. 11, 663961 (2021).
  MedlineGoogle Scholar
• 131. Qiu L, Liu F, Yi S et al. Loss of 5-hydroxymethylcytosine is an epigenetic biomarker in cutaneous T-cell lymphoma. J. Invest. Dermatol. 138(11), 2388–2397 (2018).
  Medline CASGoogle Scholar
• 132. Harro CM, Perez-Sanz J, Costich TL et al. Methyltransferase inhibitors restore SATB1 protective activity against cutaneous T cell lymphoma in mice. J. Clin. Invest. 131(3), e135711 (2021).
  Medline CASGoogle Scholar
• 133. Kohnken R, Mishra A. MicroRNAs in cutaneous T-cell lymphoma: the future of therapy. J. Invest. Dermatol. 139(3), 528–534 (2019).
  Medline CASGoogle Scholar
• 134. Ralfkiaer U, Hagedorn PH, Bangsgaard N et al. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL). Blood 118(22), 5891–5900 (2011).
  Medline CASGoogle Scholar
• 135. Sandoval J, Diaz-Lagares A, Salgado R et al. MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma. J. Invest. Dermatol. 135(4), 1128–1137 (2015).
  Medline CASGoogle Scholar
• 136. Gluud M, Willerslev-Olsen A, Gjerdrum LMR et al. MicroRNAs in the pathogenesis, diagnosis, prognosis and targeted treatment of cutaneous T-cell lymphomas. Cancers 12(5), 1229 (2020).
  Medline CASGoogle Scholar
• 137. Guo W, Liu GM, Guan JY et al. Epigenetic regulation of cutaneous T-cell lymphoma is mediated by dysregulated lncRNA MALAT1 through modulation of tumor microenvironment. Front. Oncol. 12, 977266 (2022).
  MedlineGoogle Scholar
• 138. Ralfkiaer U, Lindahl LM, Litman T et al. MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma. Anticancer Res. 34(12), 7207–7217 (2014).
  Medline CASGoogle Scholar
• 139. Fredholm S, Willerslev-Olsen A, Met O et al. SATB1 in malignant T cells. J. Invest. Dermatol. 138(8), 1805–1815 (2018).
  Medline CASGoogle Scholar
• 140. Witten L, Slack FJ. miR-155 as a novel clinical target for hematological malignancies. Carcinogenesis 41(1), 2–7 (2020).
  Medline CASGoogle Scholar
• 141. Seto AG, Beatty X, Lynch JM et al. Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma. Br. J. Haematol. 183(3), 428–444 (2018).
  Medline CASGoogle Scholar
• 142. Querfeld C, Foss FM, Pinter-Brown LC et al. Phase 1 study of the safety and efficacy of MRG-106, a synthetic inhibitor of microRNA-155, in CTCL patients. Blood 130(Suppl. 1), S820 (2017).
  Google Scholar
• 143. Berwick M, Buller DB, Cust A et al. Melanoma epidemiology and prevention. In: Melanoma. Kaufman HLMehnert JM (Eds). Springer International Publishing Cham, NY, USA, 17–49 (2016).
  Google Scholar
• 144. Saginala K, Barsouk A, Aluru JS, Rawla P, Barsouk A. Epidemiology of melanoma. Med. Sci. 9(4), 63 (2021).
  CASGoogle Scholar
• 145. American Cancer Society. Cancer Facts and Figures 2022. GA, USA (2022).
  Google Scholar
• 146. Gracia-Hernandez M, Munoz Z, Villagra A. Enhancing therapeutic approaches for melanoma patients targeting epigenetic modifiers. Cancers 13(24), 6180 (2021). •• Discusses the previous and current limitations surrounding melanoma targeted therapies with an emphasis on the promise of epigenetic drugs in combination with immunotherapies.
  Medline CASGoogle Scholar
• 147. Chatterjee A, Rodger EJ, Ahn A et al. Marked global DNA hypomethylation is associated with constitutive PD-L1 expression in melanoma. iScience 4, 312–325 (2018).
  Medline CASGoogle Scholar
• 148. Sarkar D, Leung EY, Baguley BC, Finlay GJ, Askarian-Amiri ME. Epigenetic regulation in human melanoma: past and future. Epigenetics 10(2), 103–121 (2015).
  MedlineGoogle Scholar
• 149. Micevic G, Muthusamy V, Damsky W et al. DNMT3b modulates melanoma growth by controlling levels of mTORC2 component RICTOR. Cell. Rep. 14(9), 2180–2192 (2016).
  Medline CASGoogle Scholar
• 150. Gassenmaier M, Rentschler M, Fehrenbacher B et al. Expression of DNA methyltransferase 1 is a hallmark of melanoma, correlating with proliferation and response to B-Raf and mitogen-activated protein kinase inhibition in melanocytic tumors. Am. J. Pathol. 190(10), 2155–2164 (2020).
  Medline CASGoogle Scholar
• 151. Fonsatti E, Nicolay HJ, Sigalotti L et al. Functional up-regulation of human leukocyte antigen class I antigens expression by 5-aza-2′-deoxycytidine in cutaneous melanoma: immunotherapeutic implications. Clin. Cancer Res. 13(11), 3333–3338 (2007).
  Medline CASGoogle Scholar
• 152. Triozzi PL, Aldrich W, Achberger S, Ponnazhagan S, Alcazar O, Saunthararajah Y. Differential effects of low-dose decitabine on immune effector and suppressor responses in melanoma-bearing mice. Cancer Immunol. Immunother. 61(9), 1441–1450 (2012).
  Medline CASGoogle Scholar
• 153. Emran AA, Chatterjee A, Rodger EJ et al. Targeting DNA methylation and EZH2 activity to overcome melanoma resistance to immunotherapy. Trends Immunol. 40(4), 328–344 (2019).
  Medline CASGoogle Scholar
• 154. Chiappinelli KB, Strissel PL, Desrichard A et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162(5), 974–986 (2015).
  Medline CASGoogle Scholar
• 155. Mueller DW, Rehli M, Bosserhoff AK. miRNA expression profiling in melanocytes and melanoma cell lines reveals miRNAs associated with formation and progression of malignant melanoma. J. Invest. Dermatol. 129(7), 1740–1751 (2009).
  Medline CASGoogle Scholar
• 156. Caramuta S, Egyházi S, Rodolfo M et al. MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. J. Invest. Dermatol. 130(8), 2062–2070 (2010).
  Medline CASGoogle Scholar
• 157. Chen J, Feilotter HE, Paré GC et al. MicroRNA-193b represses cell proliferation and regulates cyclin D1 in melanoma. Am. J. Pathol. 176(5), 2520–2529 (2010).
  Medline CASGoogle Scholar
• 158. Schultz J, Lorenz P, Gross G, Ibrahim S, Kunz M. MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth. Cell. Res. 18(5), 549–557 (2008).
  Medline CASGoogle Scholar
• 159. Dar AA, Majid S, De Semir D, Nosrati M, Bezrookove V, Kashani-Sabet M. miRNA-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1 protein. J. Biol. Chem. 286(19), 16606–16614 (2011).
  Medline CASGoogle Scholar
• 160. Noguchi S, Mori T, Otsuka Y et al. Anti-oncogenic microRNA-203 induces senescence by targeting E2F3 protein in human melanoma cells. J. Biol. Chem. 287(15), 11769–11777 (2012).
  Medline CASGoogle Scholar
• 161. Xu Y, Brenn T, Brown ER, Doherty V, Melton DW. Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors. Br. J. Cancer 106(3), 553–561 (2012).
  Medline CASGoogle Scholar
• 162. Liu S, Tetzlaff MT, Liu A, Liegl-Atzwanger B, Guo J, Xu X. Loss of microRNA-205 expression is associated with melanoma progression. Lab. Invest. 92(7), 1084–1096 (2012).
  Medline CASGoogle Scholar
• 163. Alegre E, Sanmamed MF, Rodriguez C, Carranza O, Martín-Algarra S, González A. Study of circulating microRNA-125b levels in serum exosomes in advanced melanoma. Arch. Pathol. Lab. Med. 138(6), 828–832 (2014).
  Medline CASGoogle Scholar
• 164. Zhang J, Lu L, Xiong Y et al. MLK3 promotes melanoma proliferation and invasion and is a target of microRNA-125b. Clin. Exp. Dermatol. 39(3), 376–384 (2014).
  Medline CASGoogle Scholar
• 165. Kappelmann M, Kuphal S, Meister G, Vardimon L, Bosserhoff AK. MicroRNA miR-125b controls melanoma progression by direct regulation of c-Jun protein expression. Oncogene 32(24), 2984–2991 (2013).
  Medline CASGoogle Scholar
• 166. Glud M, Rossing M, Hother C et al. Downregulation of miR-125b in metastatic cutaneous malignant melanoma. Melanoma Res. 20(6), 479–484 (2010).
  Medline CASGoogle Scholar
• 167. Bell RE, Khaled M, Netanely D et al. Transcription factor/microRNA axis blocks melanoma invasion program by miR-211 targeting NUAK1. J. Invest. Dermatol. 134(2), 441–451 (2014).
  Medline CASGoogle Scholar
• 168. Boyle GM, Woods SL, Bonazzi VF et al. Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor. Pigment Cell Melanoma Res. 24(3), 525–537 (2011).
  Medline CASGoogle Scholar
• 169. Levy C, Khaled M, Iliopoulos D et al. Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma. Mol. Cell 40(5), 841–849 (2010).
  Medline CASGoogle Scholar
• 170. Mazar J, Deyoung K, Khaitan D et al. The regulation of miRNA-211 expression and its role in melanoma cell invasiveness. PLOS ONE 5(11), e13779 (2010).
  MedlineGoogle Scholar
• 171. Grignol V, Fairchild ET, Zimmerer JM et al. miR-21 and miR-155 are associated with mitotic activity and lesion depth of borderline melanocytic lesions. Br. J. Cancer 105(7), 1023–1029 (2011).
  Medline CASGoogle Scholar
• 172. Satzger I, Mattern A, Kuettler U et al. microRNA-21 is upregulated in malignant melanoma and influences apoptosis of melanocytic cells. Exp. Dermatol. 21(7), 509–514 (2012).
  Medline CASGoogle Scholar
• 173. Jiang L, Lv X, Li J et al. The status of microRNA-21 expression and its clinical significance in human cutaneous malignant melanoma. Acta Histochem. 114(6), 582–588 (2012).
  Medline CASGoogle Scholar
• 174. Martin Del Campo SE, Latchana N, Levine KM et al. miR-21 enhances melanoma invasiveness via inhibition of tissue inhibitor of metalloproteinases 3 expression: in vivo effects of miR-21 inhibitor. PLOS ONE 10(1), e0115919 (2015).
  MedlineGoogle Scholar
• 175. Yang CH, Yue J, Pfeffer SR, Handorf CR, Pfeffer LM. MicroRNA miR-21 regulates the metastatic behavior of B16 melanoma cells. J. Biol. Chem. 286(45), 39172–39178 (2011).
  Medline CASGoogle Scholar
• 176. Garofalo M, Di Leva G, Romano G et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell 16(6), 498–509 (2009).
  Medline CASGoogle Scholar
• 177. Igoucheva O, Alexeev V. MicroRNA-dependent regulation of cKit in cutaneous melanoma. Biochem. Biophys. Res. Commun. 379(3), 790–794 (2009).
  Medline CASGoogle Scholar
• 178. Felicetti F, Errico MC, Bottero L et al. The promyelocytic leukemia zinc finger–microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res. 68(8), 2745–2754 (2008).
  Medline CASGoogle Scholar
• 179. Streicher KL, Zhu W, Lehmann KP et al. A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth. Oncogene 31(12), 1558–1570 (2012).
  Medline CASGoogle Scholar
• 180. Sun V, Zhou WB, Majid S, Kashani-Sabet M, Dar AA. MicroRNA-mediated regulation of melanoma. Br. J. Dermatol. 171(2), 234–241 (2014).
  Medline CASGoogle Scholar
• 181. Fattore L, Costantini S, Malpicci D et al. MicroRNAs in melanoma development and resistance to target therapy. Oncotarget 8(13), 22262–22278 (2017).
  MedlineGoogle Scholar
• 182. Latchana N, Ganju A, Howard JH, Carson WE 3rd. MicroRNA dysregulation in melanoma. Surg. Oncol. 25(3), 184–189 (2016).
  MedlineGoogle Scholar
• 183. Varrone F, Caputo E. The miRNAs role in melanoma and in its resistance to therapy. Int. J. Mol. Sci. 21(3), 878 (2020).
  Medline CASGoogle Scholar
• 184. Lorusso C, De Summa S, Pinto R, Danza K, Tommasi S. miRNAs as key players in the management of cutaneous melanoma. Cells 9(2), 415 (2020).
  Medline CASGoogle Scholar
• 185. Leucci E, Vendramin R, Spinazzi M et al. Melanoma addiction to the long non-coding RNA SAMMSON. Nature 531(7595), 518–522 (2016).
  Medline CASGoogle Scholar
• 186. Liu Y, He D, Xiao M, Zhu Y, Zhou J, Cao K. Long noncoding RNA LINC00518 induces radioresistance by regulating glycolysis through an miR-33a-3p/HIF-1α negative feedback loop in melanoma. Cell Death Dis. 12(3), 245 (2021).
  Medline CASGoogle Scholar
• 187. Li F, Li X, Qiao L, Liu W, Xu C, Wang X. MALAT1 regulates miR-34a expression in melanoma cells. Cell Death Dis. 10(6), 389 (2019).
  Medline CASGoogle Scholar
• 188. Hanniford D, Ulloa-Morales A, Karz A et al. Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis. Cancer Cell 37(1), 55–70.e15 (2020).
  Medline CASGoogle Scholar
• 189. Chen Z, Chen J, Wa Q et al. Knockdown of circ_0084043 suppresses the development of human melanoma cells through miR-429/tribbles homolog 2 axis and Wnt/β-catenin pathway. Life Sci. 243, 117323 (2020).
  Medline CASGoogle Scholar
• 190. Wang Q, Chen J, Wang A et al. Differentially expressed circRNAs in melanocytes and melanoma cells and their effect on cell proliferation and invasion. Oncol. Rep. 39(4), 1813–1824 (2018).
  Medline CASGoogle Scholar
• 191. Bachmann IM, Halvorsen OJ, Collett K et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J. Clin. Oncol. 24(2), 268–273 (2006).
  Medline CASGoogle Scholar
• 192. Mahmoud F, Shields B, Makhoul I, Hutchins LF, Shalin SC, Tackett AJ. Role of EZH2 histone methyltrasferase in melanoma progression and metastasis. Cancer Biol. Ther. 17(6), 579–591 (2016).
  Medline CASGoogle Scholar
• 193. Boumahdi S, De Sauvage FJ. The great escape: tumour cell plasticity in resistance to targeted therapy. Nat. Rev. Drug Discov. 19(1), 39–56 (2020).
  Medline CASGoogle Scholar
• 194. Zingg D, Debbache J, Schaefer SM et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat. Commun. 6, 6051 (2015).
  Medline CASGoogle Scholar
• 195. Tiffen JC, Gallagher SJ, Tseng HY, Filipp FV, Fazekas De St Groth B, Hersey P. EZH2 as a mediator of treatment resistance in melanoma. Pigment Cell Melanoma Res. 29(5), 500–507 (2016).
  Medline CASGoogle Scholar
• 196. Tiago M, Capparelli C, Erkes DA et al. Targeting BRD/BET proteins inhibits adaptive kinome upregulation and enhances the effects of BRAF/MEK inhibitors in melanoma. Br. J. Cancer 122(6), 789–800 (2020).
  Medline CASGoogle Scholar
• 197. Nikbakht N, Tiago M, Erkes DA, Chervoneva I, Aplin AE. BET inhibition modifies melanoma infiltrating T cells and enhances response to PD-L1 blockade. J. Invest. Dermatol. 139(7), 1612–1615 (2019).
  Medline CASGoogle Scholar
• 198. Rothhammer T, Bosserhoff AK. Epigenetic events in malignant melanoma. Pigment Cell Res 20(2), 92–111 (2007).
  Medline CASGoogle Scholar
• 199. Emmons MF, Faião-Flores F, Sharma R et al. HDAC8 regulates a stress response pathway in melanoma to mediate escape from BRAF inhibitor therapy. Cancer Res. 79(11), 2947–2961 (2019).
  Medline CASGoogle Scholar
• 200. Gallagher SJ, Gunatilake D, Beaumont KA et al. HDAC inhibitors restore BRAF-inhibitor sensitivity by altering PI3K and survival signalling in a subset of melanoma. Int. J. Cancer 142(9), 1926–1937 (2018).
  Medline CASGoogle Scholar
• 201. Maertens O, Kuzmickas R, Manchester HE et al. MAPK pathway suppression unmasks latent DNA repair defects and confers a chemical synthetic vulnerability in BRAF-, NRAS-, and NF1-mutant melanomas. Cancer Discov. 9(4), 526–545 (2019).
  Medline CASGoogle Scholar
• 202. Lienlaf M, Perez-Villarroel P, Knox T et al. Essential role of HDAC6 in the regulation of PD-L1 in melanoma. Mol. Oncol. 10(5), 735–750 (2016).
  Medline CASGoogle Scholar
• 203. Woan KV, Lienlaf M, Perez-Villaroel P et al. Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: enhanced antitumor immunity and impaired cell proliferation. Mol. Oncol. 9(7), 1447–1457 (2015).
  Medline CASGoogle Scholar
• 204. Woods DM, Woan K, Cheng F et al. The antimelanoma activity of the histone deacetylase inhibitor panobinostat (LBH589) is mediated by direct tumor cytotoxicity and increased tumor immunogenicity. Melanoma Res. 23(5), 341–348 (2013).
  Medline CASGoogle Scholar
• 205. Khushalani NI, Markowitz J, Eroglu Z et al. A phase I trial of panobinostat with ipilimumab in advanced melanoma. J. Clin. Oncol. 35(Suppl. 15), S9547 (2017).
  Google Scholar
• 206. Kalin JH, Wu M, Gomez AV et al. Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nat. Commun. 9(1), 53 (2018).
  MedlineGoogle Scholar
• 207. Portela A, Esteller M. Epigenetic modifications and human disease. Nat. Biotechnol. 28(10), 1057–1068 (2010).
  Medline CASGoogle Scholar
• 208. Strub T, Ghiraldini FG, Carcamo S et al. SIRT6 haploinsufficiency induces BRAF(V600E) melanoma cell resistance to MAPK inhibitors via IGF signalling. Nat. Commun. 9(1), 3440 (2018).
  MedlineGoogle Scholar
• 209. Shalem O, Sanjana NE, Hartenian E et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343(6166), 84–87 (2014).
  Medline CASGoogle Scholar
• 210. Iyer NG, Ozdag H, Caldas C. p300/CBP and cancer. Oncogene 23(24), 4225–4231 (2004).
  Medline CASGoogle Scholar
• 211. Bandyopadhyay D, Okan NA, Bales E, Nascimento L, Cole PA, Medrano EE. Down-regulation of p300/CBP histone acetyltransferase activates a senescence checkpoint in human melanocytes. Cancer Res. 62(21), 6231–6239 (2002).
  Medline CASGoogle Scholar
• 212. Kim E, Zucconi BE, Wu M et al. MITF expression predicts therapeutic vulnerability to p300 inhibition in human melanoma. Cancer Res. 79(10), 2649–2661 (2019).
  Medline CASGoogle Scholar
• 213. Wang R, He Y, Robinson V et al. Targeting lineage-specific MITF pathway in human melanoma cell lines by A-485, the selective small-molecule inhibitor of p300/CBP. Mol. Cancer Ther. 17(12), 2543–2550 (2018).
  Medline CASGoogle Scholar
• 214. Arozarena I, Wellbrock C. Phenotype plasticity as enabler of melanoma progression and therapy resistance. Nat. Rev. Cancer 19(7), 377–391 (2019).
  Medline CASGoogle Scholar
• 215. Wu H, Xu H, Jia D, Li T, Xia L. METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/β-catenin pathway. Ann.Transl. Med. 9(14), 1155 (2021).
  Medline CASGoogle Scholar
• 216. Bhattarai PY, Kim G, Poudel M, Lim S-C, Choi HS. METTL3 induces PLX4032 resistance in melanoma by promoting m6A-dependent EGFR translation. Cancer Lett. 522, 44–56 (2021).
  Medline CASGoogle Scholar