Li Zhexuan, Zhang Longbo, Liu Zhiqiang, Huang Tianxiang, Wang Ying, Ma Yujie, Fang Xingqi, He Yanqing, Zhou Yangying, Huo Lei, Wu Jun
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
J Cancer. 2020 Aug 1;11(19):5840-5851. doi: 10.7150/jca.47588. eCollection 2020.
Human glioma is the most common malignant and fatal primary tumor in the central nervous system. Currently, the high incidence and low cure rate of glioma make it a considerable threat to human health. Thus, elucidating the molecular mechanisms of glioma development and progression has become a major focus to identify new and effective biomarkers and improve the comprehensive neurosurgical treatment of glioma from the basic research and clinical perspectives. In our present study, we aimed to investigate the expression pattern and biological function of Metastasis suppressor protein 1(MTSS1) in glioma and to further explore whether miRNAs were involved in the deregulation of MTSS1. By overexpressing MTSS1 in highly malignant human glioma cells, we discovered a role for MTSS1 in suppressing the proliferation and invasion of glioma cells, and we showed that MTSS1 participated in transforming growth factor-beta 1 (TGF-β1) -induced epithelial-mesenchymal transition (EMT) in glioma cells. Biochemical analyses suggested that miR-182 may target MTSS1 and that miR-182 expression is negatively correlated with MTSS1 expression in glioma tissues. This finding was further confirmed by luciferase reporter experiments. Furthermore, a miR-182 inhibitor induced glioma cell proliferation and invasion by increasing MTSS1 expression. In conclusion, we believed that miR-182 modulates glioma cell migration and invasion by targeting the MTSS1 and suggested that miR-182 was a potential therapeutic target for gliomas.
人类胶质瘤是中枢神经系统中最常见的恶性致命原发性肿瘤。目前，胶质瘤的高发病率和低治愈率对人类健康构成了相当大的威胁。因此，从基础研究和临床角度阐明胶质瘤发生发展的分子机制，已成为识别新的有效生物标志物以及改善胶质瘤综合神经外科治疗的主要研究重点。在本研究中，我们旨在探讨转移抑制蛋白1（MTSS1）在胶质瘤中的表达模式和生物学功能，并进一步探究微小RNA（miRNA）是否参与了MTSS1的表达失调。通过在高恶性人胶质瘤细胞中过表达MTSS1，我们发现MTSS1在抑制胶质瘤细胞增殖和侵袭中发挥作用，并且表明MTSS1参与了转化生长因子-β1（TGF-β1）诱导的胶质瘤细胞上皮-间质转化（EMT）。生化分析表明，miR-182可能靶向MTSS1，并且在胶质瘤组织中miR-182表达与MTSS1表达呈负相关。荧光素酶报告基因实验进一步证实了这一发现。此外，miR-182抑制剂通过增加MTSS1表达诱导胶质瘤细胞增殖和侵袭。总之，我们认为miR-182通过靶向MTSS1调节胶质瘤细胞迁移和侵袭，并表明miR-182是胶质瘤的一个潜在治疗靶点。
