MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma

Braig, Simone and Mueller, Daniel W. and Rothhammer, Tanja and Bosserhoff, Anja-Katrin (2010) MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma. CELLULAR AND MOLECULAR LIFE SCIENCES, 67 (20). pp. 3535-3548. ISSN 1420-682X, 1420-9071

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: BONE MORPHOGENETIC PROTEINS; FIBROBLAST-GROWTH-FACTOR; MESSENGER-RNA; TUMOR-GROWTH; IN-VITRO; PROMOTES PROGRESSION; CELL-PROLIFERATION; OVARIAN-CANCER; BREAST-CANCER; INVASION; Malignant melanoma; Bone morphogenetic proteins; MicroRNA; HOX genes; Fibroblast growth factor; Migration
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Jul 2020 11:36
Last Modified: 08 Jul 2020 11:36
URI: https://pred.uni-regensburg.de/id/eprint/24047

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