Yuan Jian, Xiao Gelei, Peng Gang, Liu Dingyang, Wang Zeyou, Liao Yiwei, Liu Qing, Wu Minghua, Yuan Xianrui
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; The Institute of Skull Base Surgery & Neuro-oncology at Hunan, Changsha, Hunan 410008, PR China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
Biochem Biophys Res Commun. 2015 Feb 6;457(2):171-6. doi: 10.1016/j.bbrc.2014.12.078. Epub 2014 Dec 24.
Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, including in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3' UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells.
胶质母细胞瘤（GBM）是最致命的脑肿瘤，因为它对放疗和化疗等传统疗法具有抗性。TAZ是Hippo信号通路的重要介质，在包括GBM在内的多种癌症中被发现上调，并在肿瘤的起始和进展中发挥重要作用。然而，关于TAZ在肿瘤中表达的调控知之甚少。在本研究中，我们发现miR-125a-5p通过直接靶向TAZ的3'UTR，是胶质瘤细胞中TAZ的重要调节因子。在正常星形胶质细胞和一组胶质瘤细胞系中，miR-125a-5p水平与TAZ水平呈负相关。miR-125a-5p抑制TAZ靶基因（包括CTGF和survivin）的表达，抑制细胞增殖并诱导GBM细胞分化；而TAZ的过表达可挽救miR-125a-5p的作用。本研究揭示了胶质瘤细胞中TAZ失调的机制，也证明了miR-125a-5p在胶质母细胞瘤细胞中的肿瘤抑制作用。
