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

Zhixin Liu  ¹ , Teng Ma  ¹ , Jufeng Duan  ¹ , Xiaofei Liu  ¹ , Long Liu  ¹ Affiliations

• PMID: 33355365
• PMCID: PMC7789109
• DOI: 10.3892/mmr.2020.11793

Free PMC article

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 overexpression 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.

Keywords: colorectal cancer; F‑box and WD repeat domain containing 7; microRNA‑223; Notch pathway; Akt/mTOR pathway; proliferation; apoptosis.