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

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.