title: Lentivirus-mediated downregulation of MAT2B inhibits cell proliferation and induces apoptosis in melanoma.
abstract: Malignant melanoma is the most lethal of skin cancers and its pathogenesis is complex and heterogeneous. The efficacy of conventional therapeutic regimens for melanoma remains limited. Thus, it is important to explore novel effective therapeutic targets in the treatment of melanoma. The MAT2B gene encodes for the regulatory subunit of methionine adenosyltransferase (MAT). Recent studies have suggested that MAT2B may have functional roles other than modulating catalytic activity of MAT. In order to identify the roles of MAT2B in the tumorigenesis of malignant melanoma, we compared MAT2B expression profile in melanoma tissues with that in benign nevus samples. We employed lentivirus-mediated RNAi to downregulate the expression of MAT2B in malignant melanoma cell lines (A375 and Mel-RM), and investigated the effects of MAT2B on cell growth, colony-formation ability and apoptosis in vitro, as well as tumor growth of a xenograft model in vivo. The expression levels of BCL2 and XAF1 proteins, which were closely related to tumor cell apoptosis, were analyzed by western blot analysis. Our data showed that MAT2B was elevated in both primary and metastatic melanoma tissues compared with benign nevus samples. Lentivirus-mediated downregulation of MAT2B suppressed cell growth, colony formation and induced apoptosis in A375 and Mel-RM cell lines in vitro, affected protein expression of BCL2 and XAF1, extended the transplanted tumor growth in vivo. These results indicated that MAT2B was critical in the proliferation of melanoma cells and tumorigenicity. It may be considered as a potential anti-melanoma therapeutic target.
authors: Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Yu
authors: Y
authors: Lei
authors: Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.
authors: Bo
authors: B
authors: Zhang
authors: Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors: Yaohua
authors: Y
authors: Zhang
authors: Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Yuan
authors: Y
authors: Zhao
authors: Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Jingying
authors: J
authors: Sun
authors: Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Xuejun
authors: X
authors: Zhang
authors: Institute of Dermatology and Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors: Sen
authors: S
authors: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D008716:Methionine Adenosyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C000595707:BCL2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C417551:XAF1 protein, human; C527162:MAT2B protein, human; D008716:Methionine Adenosyltransferase