MiR-21: an environmental driver of malignant melanoma?

Journal of Translational Medicine

Bodo C Melnik¹ 

[1] Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Sedanstrasse 115, Osnabrück, 49090, Germany

关键词: Western lifestyle;    UV-irradiation;    Pollution;    Obesity;    MiR-21;    Milk;    Melanoma;    Inflammation;    Exosome;    Environment;   

Others  :  1221486
DOI  :  10.1186/s12967-015-0570-5

 received in 2015-03-01, accepted in 2015-06-10,  发布年份 2015

【 摘 要 】

Since the mid-1950’s, melanoma incidence has been rising steadily in industrialized Caucasian populations, thereby pointing to the pivotal involvement of environmental factors in melanomagenesis. Recent evidence underlines the crucial role of microRNA (miR) signaling in cancer initiation and progression. Increased miR-21 expression has been observed during the transition from a benign melanocytic lesion to malignant melanoma, exhibiting highest expression of miR-21. Notably, common BRAF and NRAS mutations in cutaneous melanoma are associated with increased miR-21 expression. MiR-21 is an oncomiR that affects critical target genes of malignant melanoma, resulting in sustained proliferation (PTEN, PI3K, Sprouty, PDCD4, FOXO1, TIPE2, p53, cyclin D1), evasion from apoptosis (FOXO1, FBXO11, APAF1, TIMP3, TIPE2), genetic instability (MSH2, FBXO11, hTERT), increased oxidative stress (FOXO1), angiogenesis (PTEN, HIF1α, TIMP3), invasion and metastasis (APAF1, PTEN, PDCD4, TIMP3). The purpose of this review is to provide translational evidence for major environmental and individual factors that increase the risk of melanoma, such as UV irradiation, chemical noxes, air pollution, smoking, chronic inflammation, Western nutrition, obesity, sedentary lifestyle and higher age, which are associated with increased miR-21 signaling. Exosomal miR-21 induced by extrinsic and intrinsic stimuli may be superimposed on mutation-induced miR-21 pathways of melanoma cells. Thus, oncogenic miR-21 signaling may be the converging point of intrinsic and extrinsic stimuli driving melanomagenesis. Future strategies of melanoma treatment and prevention should thus aim at reducing the burden of miR-21 signal transduction.

【 授权许可】

   
2015 Melnik.

【 图 表 】

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