title: DNA methylation and histone acetylation regulate the expression of MGMT and chemosensitivity to temozolomide in malignant melanoma cell lines.
abstract: Malignant melanoma is an aggressive, highly lethal dermatological malignancy. Chemoresistance and rapid metastasis limit the curative effect of multimodal therapies like surgery or chemotherapy. The suicide enzyme O6-methylguanine-DNA methyltransferase (MGMT) removes adducts from the O6-position of guanine to repair DNA damage. High MGMT expression is associated with resistance to therapy in melanoma. However, it is unknown if MGMT is regulated by DNA methylation or histone acetylation in melanoma. We examined the effects of the DNA methylation inhibitor 5-Aza-2'-deoxycytidine and histone deacetylase inhibitor Trichostatin A alone or in combination on MGMT expression and promoter methylation and histone acetylation in A375, MV3, and M14 melanoma cells. This study demonstrates that MGMT expression, CpG island methylation, and histone acetylation vary between melanoma cell lines. Combined treatment with 5-Aza-2'-deoxycytidine and Trichostatin A led to reexpression of MGMT, indicating that DNA methylation and histone deacetylation are associated with silencing of MGMT in melanoma. This study provides information on the role of epigenetic modifications in malignant melanoma that may enable the development of new strategies for treating malignant melanoma.
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.|Department of Stereotactic Radiosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Hou
authors.affiliation: Department of Dermatology, Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, 223002, China.
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Department of Stereotactic Radiosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Jiang
authors.affiliation: Department of Stereotactic Radiosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Stereotactic Radiosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
authors.forename: Shou-Xin
authors.initials: SX
authors.lastname: Feng
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
authors.forename: Yan-Qun
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China. dr.guanjiang@gmail.com.
authors.forename: Guan
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000096:biosynthesis*; D045643:DNA Repair Enzymes / Q000096:biosynthesis*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: Acetylation; MGMT; Melanoma; Methylation; Temozolomide