Xu Liang, Yu Ju, Wang Zhongyong, Zhu Qing, Wang Wenjie, Lan Qing
Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
Oncol Rep. 2017 Aug;38(2):725-734. doi: 10.3892/or.2017.5712. Epub 2017 Jun 12.
Gliomas are the most common primary central nervous system tumors and account for approximately 80% of malignant brain tumors. MicroRNAs (miRNAs) are a class of small non-coding, regulatory RNA molecules that mediate the expression levels of specific proteins. As a member of the miRNA family, miR-543 plays a tumor suppressive or an oncogenic role in different types of tumors. However, the expression and role of miR-543 in glioma remain unknown. In the present study, the expression level of miR-543 in glioma cell lines and tissues was investigated. A series of in vitro and in vivo experiments was then performed to elucidate the function of miR-543 in glioma. Moreover, proteomic profiling was applied in this study to determine the landscape of differentially expressed proteins associated with miR-543-mediated carcinogenesis in glioma. We found that the expression level of miR-543 was greatly downregulated in glioma cell lines and tissues. Furthermore, the expression level of miR-543 was negatively associated with high-grade glioma. Functional studies demonstrated that miR-543 in glioma cells induced apoptosis and inhibited growth, the cell cycle, migration and invasion. In addition, the in vivo study showed that miR-543 suppressed tumorigenicity of glioma cells. In the present study, a label-free quantitative proteomic approach was performed and 339 proteins were identified as dysregulated after miR-543 was overexpressed. Among these dysregulated proteins, 165 were upregulated and 174 were downregulated. Moreover, multiple pathways were significantly enriched and were probably involved in miR-543-mediated tumorigenesis, including RNA degradation and the inositol phosphate metabolism pathway. In conclusion, miR-543 may function as a tumor suppressor in glioma and may serve as a future therapeutic target in therapy for patients with glioma.
胶质瘤是最常见的原发性中枢神经系统肿瘤,约占恶性脑肿瘤的80%。微小RNA(miRNA)是一类小的非编码调节RNA分子,可介导特定蛋白质的表达水平。作为miRNA家族的成员,miR-543在不同类型的肿瘤中发挥肿瘤抑制或致癌作用。然而,miR-543在胶质瘤中的表达及作用尚不清楚。在本研究中,我们调查了miR-543在胶质瘤细胞系和组织中的表达水平。随后进行了一系列体外和体内实验,以阐明miR-543在胶质瘤中的功能。此外,本研究应用蛋白质组学分析来确定与miR-543介导的胶质瘤致癌作用相关的差异表达蛋白质图谱。我们发现,miR-543的表达水平在胶质瘤细胞系和组织中显著下调。此外,miR-543的表达水平与高级别胶质瘤呈负相关。功能研究表明,胶质瘤细胞中的miR-543可诱导细胞凋亡并抑制生长、细胞周期、迁移和侵袭。此外,体内研究表明,miR-543可抑制胶质瘤细胞的致瘤性。在本研究中,我们采用了无标记定量蛋白质组学方法,在miR-543过表达后,鉴定出339种蛋白质表达失调。在这些失调的蛋白质中,165种上调,174种下调。此外,多个通路显著富集,可能参与了miR-543介导的肿瘤发生,包括RNA降解和肌醇磷酸代谢通路。总之,miR-543可能在胶质瘤中发挥肿瘤抑制作用,并可能成为未来胶质瘤患者治疗的靶点。