MicroRNA-101通过靶向SOX9抑制人胶质母细胞瘤的增殖、迁移和侵袭  

MicroRNA-101 inhibits proliferation,migration and invasion of human glioblastoma by targeting SOX9

作　　者：刘楠[1] 张磊[1,2] 王震 成迎端[1,3] 张鹏幸[1] 王欣[4] 温伟红[5] 杨宏伟[4] 刘辉[1] 金卫林[6] 张永生[1] 涂艳阳[1,4] 

机构地区：[1]第四军医大学唐都医院实验外科,陕西西安710038 [2]西安儿童医院矫形外科,陕西西安710003 [3]北布伦瑞克医院研究部,新泽西美国08902 [4]哈佛医学院布莱根妇女医院神经外科,波士顿美国02115 [5]第四军医大学免疫学教研室,陕西西安710032 [6]上海交通大学电子信息与电子工程学院薄膜与微细技术教育部重点实验室仪器科学与工程中心纳米生物医学与工程研究室,上海200240

出　　处：《转化医学电子杂志》2017年第7期37-43,共7页E-Journal of Translational Medicine

基　　金：国家自然科学基金(81572983);陕西省社会发展科技攻关项目(2015SF027);唐都医院创新发展基金资助项目(2016JCYJ013)

摘　　要：多形性胶质母细胞瘤(GBM)起源于大脑皮质,是最常见的原发性恶性肿瘤.尽管当今的治疗手段不断进步,包括手术、放疗、化疗和光动力治疗等,然而GBM患者的预后情况仍然较差.最近的研究表明,microRNA-101(miR-101)在人肿瘤中显著下调,并与肿瘤细胞的增殖和肿瘤干细胞的自我更新有关.另外,miR-101在神经胶质瘤标本和细胞系中显著下调,但胶质瘤中miR-101的这种下调现象的分子机制尚不明确.本研究发现miR-101可以通过靶向SOX9在体内和体外抑制胶质瘤细胞的增殖和侵袭.沉默SOX9对胶质瘤细胞的增殖和侵袭影响与miR-101类似.qRT-PCR和Western blot检测发现在人神经胶质瘤细胞系U251MG和U87MG中miR-101与SOX9呈负相关,荧光素酶报告分析发现miR-101可以通过靶向SOX9的3’UTR区抑制SOX9的表达.研究结果表明miR-101通过靶向抑制SOX9的表达在体内和体外调节人神经胶质瘤的增殖、迁移和侵袭,说明miR-101是未来神经胶质瘤治疗的潜在靶标.Glioblastoma multiforme （GBM） is the most common primary malignant tumors originating in the brain parenchyma. At present, GBM patients have a poor prognosis despite of the con- tinuous progress in therapeutic technologies including surgery, ra- diotherapy, photodynamic therapy, and chemotherapy. Recent studies revealed that miR-101 was remarkably down-regulated in kinds of human cancers and was associated with aggressive tumor cell proliferation and stem ceil self-renewal. Data also showed that miR-101 was down-regulated in primary glioma samples and cell lines, but the underlying molecular mechanism of the deregulation of miR-101 in glioma remained largely unknown. In this study, we found that miR-101 could inhibit the proliferation and invasion of glioma cells both in vitro and in vivo by directly targeting SOX9 [ sex-determining region Y （ SRY）-box 9 protein ]. Silencing of SOX9 exerted similar effects with miR-101 overexpression on glio- ma ceils proliferation and invasion. Quantitative reverse transcrip- tion PCR and Western blotting analysis revealed a negative rela- tionship between miR-101 and SOX9 in human glioma U251MG and U87MG cells, and the luciferase assay indicated that miR- 101 altered SOX9 expression by directly targeting on 3＇UTR. Taken together, our findings suggest that miR-101 regulates glio- ma proliferation, migration and invasion via directly downregulat- ing SOX9 both in vitro and in vivo, and miR-101 may be a poten- tial therapeutic target for future glioma treatment.

关 键 词：miR-101 SOX9 侵袭 迁移 增殖 

分 类 号：R739.41[医药卫生—肿瘤]