Bu Pingyuan, Yang Ping
Department of Burns, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
Exp Ther Med. 2014 Jul;8(1):309-315. doi: 10.3892/etm.2014.1708. Epub 2014 May 12.
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.
微小RNA（miR）-203已被证明在肿瘤发生过程中发挥抑制作用。最近，有报道称miR-203在恶性黑色素瘤（MM）中起作用；然而，miR-203在MM中的详细功能仍不清楚。在本研究中，与相邻正常组织相比，MM组织中miR-203的表达明显下调。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的一个新靶点，且多功能蛋白聚糖在MM组织中的表达显著增加。抑制miR-203可增加多功能蛋白聚糖的蛋白表达，而在MM A375细胞中上调miR-203则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。本研究进一步探讨了miR-203是否参与多功能蛋白聚糖介导的A375细胞迁移，结果表明，miR-203的上调显著抑制A375细胞迁移，而多功能蛋白聚糖的过表达则削弱了这种抑制作用。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对MM细胞迁移表现出抑制作用，因此，可能成为MM转移的有效抑制剂。
