Xu Jingjing, Liu Yuqiong, Guo Si, Ma Shengli, Xiao Lin, Wei Na, Xue Rui
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Clinical Laboratory, Henan Provincial People's Hospital, 7 Wei Wu Road, Zhengzhou, 450000, China.
Mol Neurobiol. 2016 Sep;53(7):4631-7. doi: 10.1007/s12035-015-9401-1. Epub 2015 Aug 26.
Malignant astrocytomas are the most common primary brain tumors. The critical characterizes of astrocyomas are their aggressive and infiltrative in the brain, which leads to uncontrollable by conventional forms of therapy. MicroRNAs are small RNAs that had been found to regulate their targets by specific binding to the 3'-untranslated region (3'UTR) of mRNA. Recent advances in understanding the molecular biology of these tumors have revealed that microRNA (miRNA) disruption may play important roles in the pathogenesis of astrocytomas. And some of the miRNA alterations were found in the serum of astrocytoma patients. In this study, we studied the expression profile of miR-128, in the different stages of astrocytoma tissues and two human astrocytoma cell lines, A172 and T98G cells. We found that the levels of miR-128 are decreased in the A172 and T98G cells when compared to normal human astrocyte (NHA). Furthermore, the levels of miR-128 decreased gradually to the pathological stages of astrocytomas. We also identified that TROVE2 is a novel target of miR-128 by the luciferase reporter system. Furthermore, the expression levels of TROVE2 are dramatically increased with the pathological stages increasing. Finally, the levels of TROVE2 are negatively correlated with miR-128 in astrocytoma tissues. Our data provided novel evidence for the miR-128 and TROVE2 in the development of human astrocytomas.
恶性星形细胞瘤是最常见的原发性脑肿瘤。星形细胞瘤的关键特征是其在脑内具有侵袭性和浸润性,这导致常规治疗方式难以控制。微小RNA是一类小RNA,已发现它们通过与mRNA的3'-非翻译区(3'UTR)特异性结合来调控其靶标。在对这些肿瘤分子生物学的理解方面的最新进展表明,微小RNA(miRNA)的破坏可能在星形细胞瘤的发病机制中起重要作用。并且在星形细胞瘤患者的血清中发现了一些miRNA改变。在本研究中,我们研究了miR-128在不同阶段星形细胞瘤组织以及两种人星形细胞瘤细胞系A172和T98G细胞中的表达谱。我们发现,与正常人星形胶质细胞(NHA)相比,A172和T98G细胞中miR-128的水平降低。此外,miR-128的水平随着星形细胞瘤的病理阶段逐渐降低。我们还通过荧光素酶报告系统确定TROVE2是miR-128的一个新靶标。此外,TROVE2的表达水平随着病理阶段的增加而显著升高。最后,在星形细胞瘤组织中,TROVE2的水平与miR-128呈负相关。我们的数据为miR-128和TROVE2在人类星形细胞瘤发生发展中的作用提供了新的证据。