title: miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2.
abstract: It has been well documented that miRNAs can modulate the effectiveness of cancer-associated signaling pathways. Mitogen-activated protein kinase (MAPK/ERK) signaling plays an essential role in the progression of many cancers, including melanoma and colon cancers. However, no single miRNA is reported to directly target multiple components of the MAPK/ERK pathway. We performed a miRNA PCR array screening with various MAPK/ERK signaling activities. The miRNA array data revealed that the expression of miR-524-5p was decreased in cells with an active MAPK/ERK pathway and confirmed that the expression of miR-524-5p is inversely associated with the activity of the MAPK/ERK pathway. We demonstrated that miR-524-5p directly binds to the 3'-untranslated regions of both BRAFandERK2 and suppresses the expression of these proteins. Because BRAF and ERK2 are the main components of MAPK signaling, the overexpression of miR-524-5p effectively inhibits MAPK/ERK signaling, tumor proliferation, and melanoma cell migration. Moreover, tumors overexpressing miR-524-5p were significantly smaller than those of the negative control mice. Our findings provide new insight into the role of miR-524-5p as an important miRNA that negatively regulates the MAPK/ERK signaling pathway, suggesting that miR-524-5p could be a potent therapeutic candidate for melanoma treatment.
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan.
authors.forename: Szu-Mam
authors.initials: SM
authors.lastname: Liu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jean
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan. Center for Dynamical Biomarkers and Translational Medicine, National Central University, Jhongli, Taiwan. Department of Physics, Chung Yuan Christian University, Jhongli, Taiwan.
authors.forename: Hoong-Chien
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan. Center for Dynamical Biomarkers and Translational Medicine, National Central University, Jhongli, Taiwan.
authors.forename: Feng-Hsiang
authors.initials: FH
authors.lastname: Chung
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan.
authors.forename: Nianhan
authors.initials: N
authors.lastname: Ma
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; C000599909:MIRN-524 microRNA, human; C547397:MIRN214 microRNA, human; C548883:MIRN433 microRNA, human; D035683:MicroRNAs; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1