Altered expression of microRNA (miRNA) is associated with the occurrence and metastasis of various tumors. We previously found that miR-218 inhibits tumor angiogenesis through the RICTOR/VEGFA axis in prostate cancer (PCa). In this study, we determined that miR-218 also had a negative effect on cell growth, migration, and invasion ability in PCa. Our data showed that miR-218 bound to the Grb2-associated binding protein 2 (GAB2) 3'-UTR region and inhibited GAB2 expression. As a novel downstream target of miR-218, GAB2 has been reported to be involved in the occurrence and development of various human tumors, but its role in the progression and metastasis of PCa has not been addressed. We demonstrated for the first time that the expression of GAB2 in the PCa cell lines was increased, while knocking down GAB2 significantly inhibited cell growth, metastatic ability and EMT process in PCa. In addition, the recovery of GAB2 could reverse the changes in the biological function of PCa cells caused by the ectopic expression of miR-218. Mechanistically, miR-218-mediated GAB2 transcriptional suppression significantly inhibited the activity of the PI3K/AKT/GSK-3β pathway, whose abnormal activation was found to be related to the malignant progression of PCa. Taken together, our findings suggest that the miR-218/GAB2 axis may become a novel prognostic indicator and potential therapeutic target in PCa.

microRNA（miRNA）的表达改变与各种肿瘤的发生和转移有关。我们以前发现，miR-218通过RICTOR / VEGFA轴抑制前列腺癌（PCa）中的肿瘤血管生成。在这项研究中，我们确定miR-218对PCa中的细胞生长，迁移和侵袭能力也具有负面影响。我们的数据显示，miR-218与Grb2相关的结合蛋白2（GAB2）3'-UTR区结合并抑制GAB2表达。作为miR-218的新型下游靶标，据报道GAB2参与了各种人类肿瘤的发生和发展，但尚未阐明它在PCa的进展和转移中的作用。我们首次证明PCa细胞系中GAB2的表达增加，而敲低GAB2则明显抑制了细胞的生长，PCa的转移能力和EMT过程。此外，GAB2的恢复可以逆转由miR-218异位表达引起的PCa细胞生物学功能的变化。从机制上讲，miR-218介导的GAB2转录抑制显着抑制了PI3K / AKT /GSK-3β途径的活性，发现其异常激活与PCa的恶性进展有关。综上所述，我们的发现表明，miR-218 / GAB2轴可能成为PCa的新的预后指标和潜在的治疗靶标。miR-218介导的GAB2转录抑制显着抑制PI3K / AKT /GSK-3β途径的活性，发现其异常激活与PCa的恶性进展有关。综上所述，我们的发现表明，miR-218 / GAB2轴可能成为PCa的新的预后指标和潜在的治疗靶标。miR-218介导的GAB2转录抑制显着抑制PI3K / AKT /GSK-3β途径的活性，发现其异常激活与PCa的恶性进展有关。综上所述，我们的发现表明，miR-218 / GAB2轴可能成为PCa的新的预后指标和潜在的治疗靶标。