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bioRxiv · 10.1101/2020.01.27.922153

MAPK-induced miR-29 restrains melanoma progression by targeting MAFG

Vera, O.·Bok, I.·Jasani, N.·Nakamura, K.·Xu, X.·Mecozzi, N.·Karreth, F. A.
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Abstract

The tumor suppressive miR-29 family of microRNAs is encoded by two clusters, miR-29b1[~]a and miR-29b2[~]c, and is regulated by several oncogenic and tumor suppressive stimuli. Here we investigated whether oncogenic MAPK hyperactivation regulates miR-29 abundance and how this signaling axis impacts melanoma development. Using mouse embryonic fibroblasts and human melanocytes, we found that oncogenic MAPK signaling stimulates p53-independent and p53-dependent transcription of pri-miR-29b1[~]a and pri-miR-29b2[~]c, respectively. Expression analyses revealed that while pri-miR-29a[~]bl remains elevated, pri-miR-29b2[~]c levels decrease during melanoma progression. Using a rapid mouse modeling platform, we showed that inactivation of miR-29 in vivo accelerates melanoma development and decreases overall survival. We identified the transcription factor MAFG as a bona fide miR-29 target that has oncogenic potential in melanocytes and is required for growth of melanoma cells. Our findings suggest that MAPK-induced miR-29 contributes to a tumor suppressive barrier by targeting MAFG, which is overcome by attenuation of miR-29b2[~]c expression.

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Vera, O., Bok, I., Jasani, N., Nakamura, K., Xu, X., Mecozzi, N., Karreth, F. A.. 2020-01-28. MAPK-induced miR-29 restrains melanoma progression by targeting MAFG. https://doi.org/10.1101/2020.01.27.922153

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