miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2
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Szu-Mam Liu1, Jean Lu2, Hoong-Chien Lee1,3,4, Feng-Hsiang Chung1,3 and Nianhan Ma1
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
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
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.
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