Glioblastoma is the most aggressive and invasive brain tumor and has a poor prognosis; elucidating the underlying molecular mechanisms is essential to select molecular targeted therapies. Here, we investigated the effect of microRNAs on the marked invasiveness of glioblastoma. U373 glioblastoma cells were infected with 140 different microRNAs from an OncomiR library, and the effects of the invasion-related microRNAs and targeted molecules were investigated after repeated Matrigel invasion assays. Screening of the OncomiR library identified miR-23a as a key regulator of glioblastoma invasion. In six glioblastoma cell lines, a positive correlation was detected between the expression levels of miR-23a and invasiveness. A luciferase reporter assay demonstrated that homeobox D10 (HOXD10) was a miR-23a-target molecule, which was verified by high scores from both the PicTar and miRanda algorithms. Forced expression of miR-23a induced expression of invasion-related molecules, including uPAR, RhoA, and RhoC, and altered expression of glial-mesenchymal transition markers such as Snail, Slug, MMP2, MMP9, MMP14, and E-cadherin; however, these changes in expression levels were reversed by HOXD10 overexpression. Thus, miR-23a significantly promoted invasion of glioblastoma cells with polarized formation of focal adhesions, while exogenous HOXD10 overexpression reversed these phenomena. Here, we identify miR-23a-regulated HOXD10 as a pivotal regulator of invasion in glioblastoma, providing a novel mechanism for the aggressive invasiveness of this tumor and providing insight into potential therapeutic targets.

胶质母细胞瘤是最具侵袭性和侵袭性的脑肿瘤，预后较差；阐明潜在的分子机制对于选择分子靶向疗法至关重要。在这里，我们研究了microRNA对胶质母细胞瘤侵袭性的影响。用OncomiR文库中的140种不同的microRNA感染了U373胶质母细胞瘤细胞，并在重复进行Matrigel入侵试验后研究了与入侵相关的microRNA和靶向分子的作用。OncomiR文库的筛选确定miR-23a是胶质母细胞瘤侵袭的关键调节因子。在六个胶质母细胞瘤细胞系中，在miR-23a的表达水平与侵袭性之间检测到正相关。萤光素酶报告基因检测证明同源盒D10（HOXD10）是miR-23a靶分子，PicTar和miRanda算法的高分验证了这一点。强迫表达miR-23a诱导侵袭相关分子的表达，包括uPAR，RhoA和RhoC以及胶质-间质转化标记（例如Snail，Slug，MMP2，MMP9，MMP14和E-cadherin）的表达改变; 但是，这些表达水平的变化被HOXD10过表达所逆转。因此，miR-23a显着促进胶质母细胞瘤细胞的侵袭，并形成极化的粘着斑，而外源性HOXD10过表达则逆转了这些现象。在这里，我们确定了miR-23a调节的HOXD10是胶质母细胞瘤侵袭的关键调节剂，为这种肿瘤的侵袭性提供了新的机制，并为潜在的治疗靶点提供了见识。