MicroRNA-485 plays tumour-suppressive roles in colorectal cancer by directly targeting GAB2

Abstract

Colorectal cancer (CRC) is reported to be the third most common cancer and the fourth leading cause of cancer-related deaths around the world. MicroRNA-485 (miR-485) has been reported to be aberrantly expressed and play important roles in several types of human malignancy. However, the expression level, biological functions and underlying molecular mechanisms of miR-485 in CRC remain unclear. Therefore, the aim of the present study was to determine miR-485 expression levels and their clinical significance in CRC and to explore the functions and underlying mechanisms of miR-485 in this disease. In the present study, miR-485 was lowly expressed in CRC tissues and cell lines. Decreased miR-485 expression was associated with tumour size, lymph node metastasis, distant metastasis and TNM stage. Functional assays indicated that upregulation of miR-485 impaired CRC cell proliferation, invasion and induced cell apoptosis. Grb2-associated binding 2 (GAB2) was identified as a direct target of miR-485 in CRC. GAB2 was upregulated in CRC tissues and was negatively correlated with the miR-485 expression level. Furthermore, GAB2 knockdown simulated the tumour-suppressing roles of miR-485 overexpression in CRC cells. Moreover, restored GAB2 expression reversed the effects of miR-485 overexpression in CRC cells. In addition, miR-485 suppressed the AKT and ERK signalling pathways in CRC by directly targeting GAB2. Collectively, these findings demonstrate that miR-485 may play tumour suppressive roles in CRC by directly targeting GAB2 and indirectly regulating AKT and ERK signalling pathways, suggesting that miR-485 may be a potential therapeutic target for patients with this disease.