MicroRNA-203 inhibits malignant melanoma cell migration by targeting versican.

MicroRNA-203 inhibits malignant melanoma cell migration by targeting versican.
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DOI:
10.3892/etm.2014.1708
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发表时间:
2014-07
影响因子:
2.7
通讯作者:
Yang P
Yang P
中科院分区:
医学4区
文献类型:
--
作者:
Bu P;Yang P

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microRNA(miR)-203已被证明在肿瘤发生中起抑制剂的作用。近年来,miR-203在恶性黑色素瘤(malignant melanoma,MM)中发挥了重要作用,但其在MM中的具体功能尚不清楚。在本研究中,与正常邻近组织相比,MM组织中miR-203的表达显著下调。基于生物信息学预测,多功能蛋白聚糖被进一步鉴定为miR-203的新靶点,并且多功能蛋白聚糖在MM组织中的表达显著增加。在MM A375细胞中,miR-203的抑制增加多功能蛋白聚糖的蛋白表达,而miR-203的上调抑制多功能蛋白聚糖的蛋白表达。此外,多功能蛋白聚糖的上调显著促进A375细胞迁移;然而,miR-203的上调抑制A375细胞迁移。本研究进一步研究了miR-203是否参与versican介导的A375细胞迁移,结果表明miR-203的上调显著抑制了A375细胞迁移,而versican的过表达则削弱了A375细胞迁移。这些观察结果表明,多功能蛋白聚糖在miR-203介导的MM细胞迁移中作为下游效应物发挥作用。因此,结果表明miR-203通过直接靶向多功能蛋白聚糖而对MM细胞迁移表现出抑制作用,因此,miR-203可能成为MM转移的有效抑制剂。
MicroRNA (miR)-203 has been demonstrated to function as a suppressor in tumorigenesis. Recently, miR-203 was reported to play a role in malignant melanoma (MM); however, the detailed function of miR-203 in MM remains unclear. In the present study, the expression of miR-203 was shown to be significantly downregulated in MM tissues when compared with normal adjacent tissues. Based on a bioinformatic prediction, versican was further identified as a novel target of miR-203, and the expression of versican was markedly increased in MM tissues. Inhibition of miR-203 increased the protein expression of versican, while upregulation of miR-203 inhibited the protein expression of versican in MM A375 cells. In addition, the upregulation of versican significantly promoted A375 cell migration; however, upregulation of miR-203 suppressed A375 cell migration. The present study further investigated whether miR-203 was involved in versican-mediated A375 cell migration, and the results indicated that upregulation of miR-203 significantly inhibited A375 cell migration, which was impaired by overexpression of versican. These observations indicated that versican functions as a downstream effector in miR-203-mediated MM cell migration. Therefore, the results demonstrated that miR-203 exhibited an inhibitory effect on MM cell migration via directly targeting versican, thus, may become an effective inhibitor for MM metastasis.
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