title: miR-193b Regulates Mcl-1 in Melanoma.
abstract: MicroRNAs play important roles in gene regulation, and their expression is frequently dysregulated in cancer cells. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 in melanoma cells, suggesting that miR-193b could act as a tumor suppressor. Herein, we demonstrate that miR-193b also down-regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. MicroRNA microarray profiling revealed that miR-193b is expressed at a significantly lower level in malignant melanoma than in benign nevi. Consistent with this, Mcl-1 is detected at a higher level in malignant melanoma than in benign nevi. In a survey of melanoma samples, the level of Mcl-1 is inversely correlated with the level of miR-193b. Overexpression of miR-193b in melanoma cells represses Mcl-1 expression. Previous studies showed that Mcl-1 knockdown cells are hypersensitive to ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w. Similarly, overexpression of miR-193b restores ABT-737 sensitivity to ABT-737-resistant cells. Furthermore, the effect of miR-193b on the expression of Mcl-1 seems to be mediated by direct interaction between miR-193b and seed and seedless pairing sequences in the 3' untranslated region of Mcl-1 mRNA. Thus, this study provides evidence that miR-193b directly regulates Mcl-1 and that down-regulation of miR-193b in vivo could be an early event in melanoma progression.
authors: Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.
authors: Jiamin
authors: J
authors: Chen
authors: Xiao
authors: X
authors: Zhang
authors: Cindy
authors: C
authors: Lentz
authors: Marie
authors: M
authors: Abi-Daoud
authors: Geneviève C
authors: GC
authors: Paré
authors: Xiaolong
authors: X
authors: Yang
authors: Harriet E
authors: HE
authors: Feilotter
authors: Victor A
authors: VA
authors: Tron
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000037:antagonists & inhibitors; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009596:Nitrophenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C501332:ABT-737; D000964:Antimetabolites, Antineoplastic; D001713:Biphenyl Compounds; D006131:Growth Inhibitors; C579095:MCL1 protein, human; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009596:Nitrophenols; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D019938:Cyclin D1