miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2

// Szu-Mam Liu 1 , Jean Lu 2 , Hoong-Chien Lee 1,3,4 , Feng-Hsiang Chung 1,3 and Nianhan Ma 1 1 Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan 2 Genomics Research Center, Academia Sinica, Taipei, Taiwan 3 Center for Dynamical Biomarkers and Translational Medicine, National Central University, Jhongli, Taiwan 4 Department of Physics, Chung Yuan Christian University, Jhongli, Taiwan Correspondence: Nianhan Ma, email: // Keywords : miR-524-5p, melanoma, BRAF, ERK2, MAPK signaling, microRNA Received : June 20, 2014 Accepted : September 08, 2014 Published : September 08, 2014 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.