PT  - JOURNAL ARTICLE
AU  - Olga Vera
AU  - Ilah Bok
AU  - Neel Jasani
AU  - Koji Nakamura
AU  - Xiaonan Xu
AU  - Nicol Mecozzi
AU  - Ariana Angarita
AU  - Kaizhen Wang
AU  - Kenneth Y. Tsai
AU  - Florian A. Karreth
TI  - MAPK-induced miR-29 targets MAFG and suppresses melanoma development
AID  - 10.1101/2020.01.27.922153
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.27.922153
4099  - http://biorxiv.org/content/early/2020/10/22/2020.01.27.922153.short
4100  - http://biorxiv.org/content/early/2020/10/22/2020.01.27.922153.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.