MicroRNA-223-induced inhibition of the FBXW7 gene affects the proliferation and apoptosis of colorectal cancer cells via the Notch and Akt/mTOR pathways

Abstract

The tumour suppressor gene F-box and WD repeat domain-containing 7 (FBXW7) plays an important role in human cancer by regulating cell division, proliferation and differentiation. However, the exact regulatory mechanisms of microRNA (miR)-223 in colorectal cancer (CRC) cells are still unknown. The present study aimed to investigate the effect and mechanism of miR-223 inhibiting FBXW7 on the proliferation and apoptosis of CRC cells. HCT116 cells were transfected with miR-223 mimics or small interfering RNA (siRNA) targeting FBXW7 (siFBXW7), and the effects of these treatments on cell proliferation and apoptosis were examined. The downstream Notch and Akt/mTOR pathways were also assessed. Following miR-223 overexpression, the mRNA and protein expression levels of FBXW7 were downregulated. Transfection with miR-223 mimics or siFBXW7 promoted the proliferation of HCT116 cells and inhibited apoptosis by promoting the Notch and Akt/mTOR signalling pathways. Conversely, miR-223 mimics transfection with FBXW7 over- expression inhibited cell viability and restored apoptosis. Thus, the present study demonstrated that miR-223 could bind to the FBXW7 gene and inhibit its expression, ultimately increasing the proliferation and preventing the apoptosis of CRC cells through the Notch and Akt/mTOR signalling pathways.