miR-145靶向调控DAB2对前列腺癌PC3细胞迁移和侵袭能力的影响

已有研究表明, miR-145在多种肿瘤中低表达, 并与细胞增殖和转移相关。文章通过生物信息学分析并结合体外实验鉴定, 发现DAB2(Disabled homolog 2)为miR-145在肿瘤转移过程中累及的新靶点。DAB2一直被认为是一个重要的抑癌基因, 在多种肿瘤标本中表达低下。然而, 研究发现, 在具高侵袭能力的前列腺癌细胞株PC3中DAB2基因却呈较高水平表达。另外, 外源表达miR-145能显著下调 DAB2表达水平, 并抑制PC3细胞的迁移和侵袭能力, 且这种miR-145诱导的PC3细胞功能缺陷能被DAB2过表达修复。上述结果表明, miR-145能通过靶向调控DAB2而影响高侵袭前列腺癌细胞的迁移和侵袭能力。

Effects of miR-145 on the migration and invasion of prostate cancer PC3 cells by targeting DAB2

It was reported that miR-145, which is significantly decreased in a variety of tumor cells, is associated with cell proliferation and metastasis. In this study, using bioinformatics analysis and in vitro assays, we identified DAB2 (Disabled homolog 2) as a downstream target gene of miR-145 during tumor metastasis process. DAB2 has been characterized as an important tumor suppressor, and is usually expressed at low levels in tumor cells. However, in this study, the relative high-level expression of DAB2 gene was observed in the highly invasive prostate cancer PC3 cells. Moreover, enforced expression of miR-145 could significantly down-regulate the expression level of DAB2 in PC3 cells, and inhibit the migration and invasion of PC3 cells. Notably, dysfunction of PC3 cells induced by miR-145 overexpression can be rescued by co-overexpression of DAB2. These results demonstrate that miR-145 regulates the migration and invasion of highly invasive prostate cancer cells through targeting DAB2 gene.