Xin Liu , Junling Zhao , PengFei Dong , Xinyuan Du , Wenpeng Lu , Yan Feng , Liqun Wang
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引用次数: 0
摘要
胶质瘤是最常见的原发性中枢神经系统(CNS)癌症,总生存率较低。迫切需要对针对胶质瘤关键因素的分子治疗进行更多的研究。本研究旨在评估TRIM6 (tripartite motif protein 6)对胶质瘤的影响。利用公共数据库,我们发现神经胶质瘤组织中TRIM6表达的增加与最差的总生存率有关。沉默TRIM6可促进胶质瘤细胞增殖、迁移和血管生成,提示TRIM6对胶质瘤有促进作用。敲低TRIM6表达可下调脑胶质瘤细胞中叉头盒M1 (FOXM1)和血管内皮生长因子A (VEGFA)的表达水平。随后,TRIM6对VEGFA表达的影响通过FOXM1调控。VEGFA过表达逆转了沉默TRIM6导致的胶质瘤细胞增殖、迁移和血管生成能力的下降。此外,我们还发现TRIM6促进了异种移植小鼠模型中胶质瘤的生长。综上所述,TRIM6表达升高与胶质瘤患者预后不良有关。TRIM6通过FOXM1-VEGFA通路促进胶质瘤细胞增殖、迁移和血管生成。因此,TRIM6作为一种新的治疗靶点,具有在临床上被探索的潜力。
TRIM6 silencing for inhibiting growth and angiogenesis of gliomas by regulating VEGFA
Gliomas are the highest prevalent primary central nervous system (CNS) cancers with poor overall survival rate. There is an urgent need to conduct more research into molecular therapies targeting critical elements of gliomas. This study herein targeted to assess the impact of tripartite motif protein 6 (TRIM6) on gliomas. Using public databases, we found the increased TRIM6 expression in tissues of glioma which was linked with worst overall survival. Silencing TRIM6 promoted glioma cell proliferation, migration and angiogenesis, suggesting the promoting effects of TRIM6 on gliomas. Knockdown of TRIM6 expression downregulated the expression levels of Forkhead box M1 (FOXM1) and vascular endothelial growth factor A (VEGFA) in glioma cells. Afterwards, impact of TRIM6 on VEGFA expression was regulated by FOXM1. VEGFA overexpression reversed the decreased abilities of glioma cell proliferation, migration and angiogenesis caused by silencing TRIM6. Furthermore, we also found that TRIM6 promoted the growth of gliomas in the xenograft mouse model. In summary, the expression of TRIM6 was increased which was related to poor prognosis of glioma patients. TRIM6 promoted glioma cell proliferation, migration and angiogenesis through the FOXM1-VEGFA pathway. Therefore, TRIM6 carries capacity to be explored as a novel therapeutic target in clinical.
期刊介绍:
The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches.
Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples.
The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.