Browsing by Subject "microRNA-31"

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    Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma
    (Impact Journals, 2015) Rajbhandari, Rajani; McFarland, Braden C.; Patel, Ashish; Gerigk, Magda; Gray, Kenneth; Fehling, Samuel C.; Bredel, Markus; Berbari, Nicolas F.; Kim, Hyunsoo; Marks, Margaret P.; Meares, Gordon P.; Sinha, Tanvi; Chuang, Jeffrey; Benveniste, Etty N.; Nozell, Susan E.; Biology, School of Science
    Glioblastomas (GBMs) are deadly tumors of the central nervous system. Most GBM exhibit homozygous deletions of the CDKN2A and CDKN2B tumor suppressors at 9p21.3, although loss of CDKN2A/B alone is insufficient to drive gliomagenesis. MIR31HG, which encodes microRNA-31 (miR-31), is a novel non-coding tumor suppressor positioned adjacent to CDKN2A/B at 9p21.3. We have determined that miR-31 expression is compromised in >72% of all GBM, and for patients, this predicts significantly shortened survival times independent of CDKN2A/B status. We show that miR-31 inhibits NF-κB signaling by targeting TRADD, its upstream activator. Moreover, upon reintroduction, miR-31 significantly reduces tumor burden and lengthens survival times in animal models. As such, our work identifies loss of miR-31 as a novel non-coding tumor-driving event in GBM.
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    MicroRNA-31 is required for astrocyte specification
    (Wiley, 2018-05) Meares, Gordon P.; Rajbhandari, Rajani; Gerigk, Magda; Tien, Chih-Liang; Chang, Chenbei; Fehling, Samuel C.; Rowse, Amber; Mulhern, Kayln C.; Nair, Sindhu; Gray, G. Kenneth; Berbari, Nicolas F.; Bredel, Markus; Benveniste, Etty N.; Nozell, Susan E.; Biology, School of Science
    Previously, we determined microRNA-31 (miR-31) is a noncoding tumor suppressive gene frequently deleted in glioblastoma (GBM); miR-31 suppresses tumor growth, in part, by limiting the activity of NF-κB. Herein, we expand our previous studies by characterizing the role of miR-31 during neural precursor cell (NPC) to astrocyte differentiation. We demonstrate that miR-31 expression and activity is suppressed in NPCs by stem cell factors such as Lin28, c-Myc, SOX2 and Oct4. However, during astrocytogenesis, miR-31 is induced by STAT3 and SMAD1/5/8, which mediate astrocyte differentiation. We determined miR-31 is required for terminal astrocyte differentiation, and that the loss of miR-31 impairs this process and/or prevents astrocyte maturation. We demonstrate that miR-31 promotes astrocyte development, in part, by reducing the levels of Lin28, a stem cell factor implicated in NPC renewal. These data suggest that miR-31 deletions may disrupt astrocyte development and/or homeostasis.