Knockdown of USP39 induces cell cycle arrest and apoptosis in melanoma.
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.
['Zhao|Yuan|Y|', 'Zhang|Bo|B|', 'Lei|Yu|Y|', 'Sun|Jingying|J|', 'Zhang|Yaohua|Y|', 'Yang|Sen|S|', 'Zhang|Xuejun|X|']
D000328:Adult D000368:Aged D000818:Animals D017209:Apoptosis D059447:Cell Cycle Checkpoints 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 D006801:Humans D007150:Immunohistochemistry D016086:Lentivirus D020935:MAP Kinase Signaling System D008297:Male D008545:Melanoma D051379:Mice D008875:Middle Aged D060787:Neoplasm Grading D009361:Neoplasm Invasiveness D009367:Neoplasm Staging D034741:RNA, Small Interfering D014161:Transduction, Genetic D047368:Tumor Burden D064570:Ubiquitin-Specific Proteases D015854:Up-Regulation D023041:Xenograft Model Antitumor Assays
USP39 Cell cycle arrest Apoptosis Melanoma ERK