Ben-Hamo Rotem, Zilberberg Alona, Cohen Helit, Efroni Sol
The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan, Israel.
Oncotarget. 2016 Apr 26;7(17):23170-81. doi: 10.18632/oncotarget.6687.
Glioblastoma Multiforme (GBM) is the most common and lethal primary tumor of the brain. GBM is associated with one of the worst 5-year survival rates among all human cancers, despite much effort in different modes of treatment.
Here, we demonstrate specific GBM cancer phenotypes that are governed by modifications to the MAPAKAP network. We then demonstrate a novel regulation mode by which a set of five key factors of the MAPKAP pathway are regulated by the same microRNA, hsa-miR-9.We demonstrate that hsa-miR-9 overexpression leads to MAPKAP signaling inhibition, partially by interfering with the MAPK14/MAPKAP3 complex. Further, hsa-miR-9 overexpression initiates re-arrangement of actin filaments, which leads us to hypothesize a mechanism for the observed phenotypic shift.
The work presented here exposes novel microRNA features and situates hsa-miR-9 as a therapeutic target, which governs metastasis and thus determines prognosis in GBM through MAPKAP signaling.
多形性胶质母细胞瘤(GBM)是最常见且致命的原发性脑肿瘤。尽管在不同治疗方式上付出了诸多努力,但GBM在所有人类癌症中的5年生存率仍处于最差之列。
在此,我们展示了由MAPAKAP网络修饰所调控的特定GBM癌症表型。然后,我们展示了一种新的调控模式,即一组五个关键的MAPKAP通路因子受同一微小RNA(hsa-miR-9)调控。我们证明hsa-miR-9过表达会导致MAPKAP信号抑制,部分原因是干扰了MAPK14/MAPKAP3复合物。此外,hsa-miR-9过表达引发肌动蛋白丝的重新排列,这使我们推测出观察到的表型转变的机制。
本文所呈现的工作揭示了新的微小RNA特征,并将hsa-miR-9定位为一个治疗靶点,它通过MAPKAP信号调控转移,从而决定GBM的预后。