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MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma
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MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma
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MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma
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Journal Article
MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma
2010
Overview
Since bone morphogenetic proteins (BMPs) play an important role in melanoma progression, we aimed to determine the molecular mechanisms leading to overexpression of BMP4 in melanoma cells compared to normal melanocytes. With our experimental approach we revealed that loss of expression of a microRNA represents the starting point for a signaling cascade finally resulting in overexpression of BMP4 in melanoma cells. In detail, strongly reduced expression of the microRNA miR-196a in melanoma cells compared to healthy melanocytes leads to enhanced HOX-B7 mRNA and protein levels, which subsequently raise Ets-1 activity by inducing basic fibroblast growth factor (bFGF). Ets-1 finally accounts for induction of BMP4 expression. We were furthermore able to demonstrate that bFGF-mediated induction of migration is achieved via activation of BMP4, thus determining BMP4 as major modulator of migration in melanoma. In summary, our study provides insights into the early steps of melanoma progression and might thereby harbor therapeutic relevance.
Publisher
Basel : SP Birkhäuser Verlag Basel,SP Birkhäuser Verlag Basel,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Bone morphogenetic protein 4
/ Bone Morphogenetic Protein 4 - genetics
/ Bone Morphogenetic Protein 4 - metabolism
/ Fibroblast Growth Factor 2 - genetics
/ Fibroblast Growth Factor 2 - metabolism
/ Gene Expression Regulation, Neoplastic
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humans
/ Melanoma
/ MicroRNA
/ miRNA
/ mRNA
/ Proteins
/ Proto-Oncogene Protein c-ets-1 - genetics
/ Proto-Oncogene Protein c-ets-1 - metabolism
/ RNA
