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

Szu Mam Liu, Jean Lu, Hoong Chien Lee, Feng Hsiang Chung, Nianhan Ma

研究成果: 雜誌貢獻期刊論文同行評審

63 引文 斯高帕斯(Scopus)

摘要

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 BRAF and ERK2 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.

原文???core.languages.en_GB???
頁(從 - 到)9444-9459
頁數16
期刊Oncotarget
5
發行號19
DOIs
出版狀態已出版 - 2014

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