Meng Delong, Chen Yuanyuan, Yun Dapeng, Zhao Yingjie, Wang Jingkun, Xu Tao, Li Xiaoying, Wang Yuqi, Yuan Li, Sun Ruochuan, Song Xiao, Huai Cong, Hu Lingna, Yang Song, Min Taishan, Chen Juxiang, Chen Hongyan, Lu Daru
State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Oncotarget. 2015 Mar 10;6(7):4901-19. doi: 10.18632/oncotarget.3208.
Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma. Three independent cohorts, the Chinese tissue microarray (TMA) cohort (N = 209), the Repository for Molecular Brain Neoplasia Data (Rembrandt) cohort (N = 371) and The Cancer Genome Atlas (TCGA) cohort (N = 528 or 396) were employed. Transcriptional or protein levels of NMI expression were significantly increased according to tumor grade in all three cohorts. High expression of NMI predicted significantly unfavorable clinical outcome for GBM patients, which was further determined as an independent prognostic factor. Additionally, expression and prognostic value of NMI were associated with molecular features of GBM including PTEN deletion and EGFR amplification in TCGA cohort. Furthermore, overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. These data demonstrate that NMI may serve as a novel prognostic biomarker and a potential therapeutic target for glioblastoma.
神经胶质瘤是最恶性的脑肿瘤，胶质母细胞瘤（GBM）是最具侵袭性的类型。N - myc（和STAT）相互作用因子（NMI）在肿瘤发生中的作用曾有零星报道，但远未阐明。本研究旨在探究NMI在人类神经胶质瘤中的作用。采用了三个独立队列，即中国组织微阵列（TMA）队列（N = 209）、分子脑肿瘤数据储存库（Rembrandt）队列（N = 371）和癌症基因组图谱（TCGA）队列（N = 528或396）。在所有三个队列中，NMI表达的转录水平或蛋白水平均随肿瘤分级显著升高。NMI高表达预示GBM患者的临床结局显著不良，这进一步被确定为一个独立的预后因素。此外，在TCGA队列中，NMI的表达及预后价值与GBM的分子特征相关，包括PTEN缺失和EGFR扩增。此外，NMI的过表达或缺失揭示了其对G1/S期进程和细胞增殖的调控作用（体外和体内均如此），且这种作用部分依赖于与NMI相互作用并受其调控的STAT1。这些数据表明，NMI可能作为胶质母细胞瘤一种新的预后生物标志物和潜在的治疗靶点。
