title: Knockdown of USP39 induces cell cycle arrest and apoptosis in melanoma.
abstract: The spliceosome machinery composed of multimeric protein complexes guides precursor messenger RNAs (mRNAs) (pre-mRNAs) splicing in eukaryotic cells. Spliceosome components have been shown to be downregulated in cancer and could be a promising molecular target for anticancer therapy. The ubiquitin-specific protease 39 (USP39) is essential for pre-mRNA splicing, and upregulated USP39 expression is noted in a variety of cancers. However, the role of USP39 in the development and progression of melanoma remains unclear. In the present study, USP39 expression was found to be increased in melanoma tissues compared with that in nevus tissues. USP39 silencing via lentivirus-mediated short hairpin RNA (shRNA) significantly suppressed melanoma cell proliferation, induced G0/G1 cell cycle phase arrest, and increased apoptosis in vitro. Moreover, USP39 knockdown suppressed melanoma tumor growth in a xenograft model. In addition, USP39 silencing was associated with the increased expressions of p21, p27, and Bax. Furthermore, the inhibition of USP39 expression decreased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, indicating that ERK signaling pathways might be involved in the regulation of melanoma cell proliferation by USP39. Our findings suggest that USP39 may play crucial roles in the development and pathogenesis of melanoma, and it may serve as a potential therapeutic target for melanoma.
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui Province, 230032, China.|Key Laboratory of Dermatology, Ministry of Education, China, Anhui Medical University, Hefei, Anhui Province, 230032, China.|Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui Province, 230032, China.|Department of Thoracic Surgery, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Oncology, the Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230601, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui Province, 230032, China.|Key Laboratory of Dermatology, Ministry of Education, China, Anhui Medical University, Hefei, Anhui Province, 230032, China.|Department of Oncology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui Province, 230032, China.|Key Laboratory of Dermatology, Ministry of Education, China, Anhui Medical University, Hefei, Anhui Province, 230032, China.|Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Jing'an District, Shanghai, 200040, China. yvonne_zhang@ymail.com.|Worldwide Medical Center, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Jing'an District, Shanghai, 200040, China. yvonne_zhang@ymail.com.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui Province, 230032, China.|Key Laboratory of Dermatology, Ministry of Education, China, Anhui Medical University, Hefei, Anhui Province, 230032, China.|Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui Province, 230032, China. ayzxj@vip.sina.com.|Key Laboratory of Dermatology, Ministry of Education, China, Anhui Medical University, Hefei, Anhui Province, 230032, China. ayzxj@vip.sina.com.|Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui Province, 230032, China. ayzxj@vip.sina.com.|Institute of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Jing'an District, Shanghai, 200040, China. ayzxj@vip.sina.com.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D020935:MAP Kinase Signaling System; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D034741:RNA, Small Interfering / Q000235:genetics; D014161:Transduction, Genetic; D047368:Tumor Burden; D064570:Ubiquitin-Specific Proteases / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; C579218:USP39 protein, human; D064570:Ubiquitin-Specific Proteases
keywords: Apoptosis; Cell cycle arrest; ERK; Melanoma; USP39