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

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)9444-9459
Number of pages16
JournalOncotarget
Volume5
Issue number19
DOIs
StatePublished - 2014

Keywords

  • BRAF
  • ERK2
  • MAPK signaling
  • Melanoma
  • MicroRNA
  • miR-524-5p

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