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.

MicroRNA-524-5p suppresses the growth and invasive abilities of gastric cancer cells

“…The present study demonstrated that the expression levels of miR-524-5p were downregulated in gastric cancer tissues and cell lines, suggesting that miR-524-5p functions as a tumor suppressor in human gastric cancer, which is consistent with previous studies (24).…”

“…Dysregulation of miR-524-5p is a frequent event in several types of cancer, including a reduction in the expression of miR-524-5p in melanoma (10) and glioma cells (9). The present study demonstrated that the expression levels of miR-524-5p were downregulated in gastric cancer tissues and cell lines, suggesting that miR-524-5p functions as a tumor suppressor in human gastric cancer, which is consistent with previous studies (24).…”

“…Previous studies have investigated the role of miRNA-524-5p (miR-524-5p) in various types of cancer. Chen et al (9) demonstrated that miR-524-5p was associated with overall survival rate and pathological grade of patients with glioma, and Liu et al (10) revealed that the expression of miR-524-5p was reduced in human melanoma, while overexpression of miR-524-5p effectively inhibited melanoma cell proliferation and migration. Furthermore, Liu et al (10) demonstrated that tumors overexpressing miR-524-5p were significantly smaller than those displayed by negative control mice.…”

Identification of plasma microRNAs as new potential biomarkers with high diagnostic power in human cutaneous melanoma

“…A possible tumor suppressor role for miR-524-5p may be in line with findings of this study showing how circulating miR-524-5p levels were significantly lower in plasma of patients compared with healthy controls. Preclinical data demonstrating that miR-524-5p overexpression inhibited melanoma cell proliferation and migration in human melanoma cell lines 51 are likely to support this notion.…”

Noncoding RNAs Regulating Cancer Signaling Network

“…MiR-524-5p has been shown to suppress melanoma cell proliferation, migration, and tumor formation by targeting multiple downstream effectors in the Ras/Raf/ERK pathway, including both Braf and ERK2. Interestingly, activation of the Ras/Raf/ERK pathway by growth-factor stimulation or overexpression of the constitutively active mutant V600E Braf results in decreased expression of miR-524-5p, suggesting a feedback loop affecting this signal regulation [ 32 ]. Besides miR-524-5p, other miRNAs such as miR-7 have also been implicated in targeting Raf in glioblastoma and adrenocortical carcinoma to dampen the downstream Ras signal [ 33 , 34 ].…”