miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth

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miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth

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Title: miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth
Author: Fulciniti, M; Amodio, N; Bandi, R L; Cagnetta, A; Samur, M K; Acharya, C; Prabhala, R; D'Aquila, P; Bellizzi, D; Passarino, G; Adamia, S; Neri, A; Hunter, Z R; Treon, S P; Anderson, K C; Tassone, P; Munshi, N C

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Citation: Fulciniti, M., N. Amodio, R. L. Bandi, A. Cagnetta, M. K. Samur, C. Acharya, R. Prabhala, et al. 2016. “miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth.” Blood Cancer Journal 6 (1): e380. doi:10.1038/bcj.2015.106. http://dx.doi.org/10.1038/bcj.2015.106.
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Abstract: Deregulated microRNA (miR)/transcription factor (TF)-based networks represent a hallmark of cancer. We report here a novel c-Myc/miR-23b/Sp1 feed-forward loop with a critical role in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell growth and survival. We have found miR-23b to be downregulated in MM and WM cells especially in the presence of components of the tumor bone marrow milieu. Promoter methylation is one mechanism of miR-23b suppression in myeloma. In gain-of-function studies using miR-23b mimics-transfected or in miR-23b-stably expressing MM and WM cell lines, we observed a significant decrease in cell proliferation and survival, along with induction of caspase-3/7 activity over time, thus supporting a tumor suppressor role for miR-23b. At the molecular level, miR-23b targeted Sp1 3′UTR and significantly reduced Sp1-driven nuclear factor-κB activity. Finally, c-Myc, an important oncogenic transcription factor known to stimulate MM cell proliferation, transcriptionally repressed miR-23b. Thus MYC-dependent miR-23b repression in myeloma cells may promote activation of oncogenic Sp1-mediated signaling, representing the first feed-forward loop with critical growth and survival role in myeloma.
Published Version: doi:10.1038/bcj.2015.106
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742623/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:25658328
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