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微小RNA-203通过靶向多功能蛋白聚糖抑制恶性黑色素瘤细胞迁移。

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

作者信息

Bu Pingyuan, Yang Ping

机构信息

Department of Burns, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

出版信息

Exp Ther Med. 2014 Jul;8(1):309-315. doi: 10.3892/etm.2014.1708. Epub 2014 May 12.

Abstract

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.

摘要

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。

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