ROCK1, a novel target of miR-145, promotes glioma cell invasion
ROCK1, a novel target of miR-145, promotes glioma cell invasion
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DOI：
10.3892/mmr.2014.1982
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发表时间：
2014-05-01
影响因子：
3.4
通讯作者：
Jiang, Bing
中科院分区：
文献类型：
--
作者：
Wan, Xin;Cheng, Quan;Jiang, Bing
恶性胶质瘤是中枢神经系统最常见的肿瘤类型，具有高度侵袭性的特点。Rho相关蛋白激酶（ROCK 1）是肌动蛋白细胞骨架重组的关键调节因子，而肌动蛋白细胞骨架重组是与癌细胞侵袭密切相关的过程。microRNA-145（miRNA-145）最近已被证明在几种类型的肿瘤（包括胶质瘤）中起抑制作用。然而，miR-145抑制胶质瘤的确切调控机制仍有待揭示。在这项研究中，我们报告说，miR-145水平显着降低，在胶质瘤组织和人类胶质瘤细胞系U87和U251，与匹配的相邻和正常脑组织相比。然后，我们将ROCK 1基因鉴定为miR-145的新靶点。ROCK 1在胶质瘤组织、U87和U251细胞中表达明显上调。此外，miR-145显著抑制U87细胞中ROCK 1蛋白的表达。我们进一步表明，miR-145转染显著降低了U87细胞的侵袭能力，并伴随着基质金属蛋白酶2和9的下调，这种作用可以通过ROCK 1的过表达来减弱。总之，本研究表明，miR-145可以抑制U87胶质瘤细胞的侵袭，至少部分通过下调RhoA/ROCK 1通路。总之，这是第一项研究报告ROCK 1作为miR-145的新靶点，作为胶质瘤细胞侵袭的正调节因子。因此，ROCK 1可能成为胶质瘤治疗的一个有希望的靶点。
Malignant glioma is the most common type of cancer in the central nervous system, with highly invasive characteristics. The Rho-associated protein kinase (ROCK1) has been found to act as key regulator of actin cytoskeleton reorganization, a process closely associated with cancer cell invasion. microRNA-145 (miRNA-145) has been recently shown to act as a suppressor in several types of tumor, including glioma. However, the exact regulatory mechanism by which miR-145 inhibits glioma still remains to be uncovered. In this study, we report that the miR-145 level was significantly reduced in glioma tissues and in the human glioma cell lines U87 and U251, as compared to matched adjacent and normal brain tissues. We then identified the ROCK1 gene as a novel target of miR-145. The expression of ROCK1 was markedly upregulated in glioma tissues, as well as in U87 and U251 cells. Moreover, miR-145 significantly inhibited ROCK1 protein expression in U87 cells. We further show that miR-145 transfection considerably reduced the invasive ability of U87 cells, and was accompanied by the downregulation of matrix metalloproteinase 2 and 9, an effect which could be attenuated by overexpression of ROCK1. In conclusion, the present study suggests that miR-145 can inhibit U87 glioma cell invasion, at least partially via downregulation of the RhoA/ROCK1 pathway. In conclusion, this is the first study to report that ROCK1, as a novel target of miR-145, acts as a positive regulator of glioma cell invasion. Therefore, ROCK1 may constitute a promising target for glioma treatment.