Wang Ze-You, Xiong Jing, Zhang Shan-Shan, Wang Jian-Jun, Gong Zhao-Jian, Dai Min-Hui
Department of Clinical Laboratory, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Ophthalmology, Xiangya Hospital, Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
Cell Mol Neurobiol. 2016 Nov;36(8):1303-1310. doi: 10.1007/s10571-016-0328-5. Epub 2016 Feb 15.
Glioblastoma multiforme (GBM) is the most common and lethal type of primary malignant brain tumor. In recent years, increasing reports suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for human cancers, including GBM. The expression and roles of microRNA-183 (miR-183) has been explored in several types of human cancers, including in GBM, and plays important roles in tumor initiation and progression. However, its biological functions in GBM remain largely unknown. In this study, we demonstrated that miR-183 was significantly up-regulated in astrocytoma tissues and glioblastoma cell lines. Introduction of miR-183 mimics into U251 cells could promoted, while its antisense oligos inhibited cell proliferation and invasion. Moreover, we identified neurofilament light polypeptide (NEFL) as a novel target gene of miR-183. The expression levels of NEFL are inversely correlated with that of miR-183 in human astrocytoma clinical specimens. In addition, NEFL-siRNA could significantly attenuate the inhibitory effects of knockdown miR-183 on the proliferation and invasion of U251 cells via mTOR signaling pathway. Overall, This study revealed that miR-183 promotes glioma cell proliferation by targeting NEFL, and also demonstrated that miR-183 could be a potential target for GBM treatment.
多形性胶质母细胞瘤(GBM)是最常见且致命的原发性恶性脑肿瘤类型。近年来,越来越多的报道表明,微小RNA(miRNA)的发现可能为包括GBM在内的人类癌症提供新的治疗靶点。微小RNA-183(miR-183)在包括GBM在内的几种人类癌症中的表达及作用已得到研究,其在肿瘤起始和进展中发挥重要作用。然而,其在GBM中的生物学功能仍 largely unknown。在本研究中,我们证明miR-183在星形细胞瘤组织和胶质母细胞瘤细胞系中显著上调。将miR-183模拟物导入U251细胞可促进其增殖,而其反义寡核苷酸则抑制细胞增殖和侵袭。此外,我们鉴定出神经丝轻链多肽(NEFL)是miR-183的一个新靶基因。在人类星形细胞瘤临床标本中,NEFL的表达水平与miR-183的表达水平呈负相关。此外,NEFL-siRNA可通过mTOR信号通路显著减弱敲低miR-183对U251细胞增殖和侵袭的抑制作用。总体而言,本研究揭示miR-183通过靶向NEFL促进胶质瘤细胞增殖,还证明miR-183可能是GBM治疗的一个潜在靶点。