Inhibition of microRNA-300 inhibits cell adhesion, migration, and invasion of prostate cancer cells by promoting the expression of DAB1.

ABSTRACT

Prostate cancer (PC) is the most common malignancy in men. As per recent findings, microRNA-300 (miR-300) were found to be overexpressed in numerous types of cancers. In this study, we aimed to explore the effects of miR-300 on the adhesion, invasion, and migration of PC cells by targeting Disabled 1 (DAB1). Firstly, the regulatory role of miRNAs on DAB1 was predicted by screening PC-related differentially expressed genes (DEGs). Immunohistochemistry was applied to determine the positive protein expression of DAB1, after which the target relationship between miR-300 and DAB1 was examined. Loss-of-function and gain-of-function experiments were conducted to determine cell proliferation, adhesion, migration, invasion capability, and cell cycle of PC cells. Our data illustrated that DAB1 had a low expression, while miR-300 was expressed at a relatively high level in PC tissues. Moreover, our clinicopathological analysis revealed that there was a correlation between miR-300 and tumor, node, metastases stage, Gleason score, and lymph node metastasis of PC patients. DAB1 was also found to be poorly expressed in PC based on the findings from the microarray analysis. The results from dual-luciferase reporter gene assay corroborated that miR-300 interacts with DAB1. Importantly, overexpression of miR-300 and/or si-DAB1 resulted in the enhancement of RAC1, MMP2, MMP9, CyclinD1, and CyclinE expressions, whereas the expression of DAB1 and Rap was reduced in PC cells, thus suggesting that down-regulated miR-300 suppressed proliferation, adhesion, migration, and invasion of PC cells. Collectively, our results provided evidence that down-regulation of miR-300 inhibits the adhesion, migration, and invasion of PC cells.