BioScience Trends. 2019;13(6):523-529. (DOI: 10.5582/bst.2019.01289)
IFITM3 upregulates c-myc expression to promote hepatocellular carcinoma proliferation via the ERK1/2 signalling pathway.
Min J, Hu J, Luo C, Zhu J, Zhao J, Zhu Z, Wu L, Yuan R
Interferon-induced transmembrane protein 3 (IFITM3) is associated with cancer development. Proto-oncogene c-myc can promote tumor proliferation. However, collections of IFITM3 and c-myc in hepatocellular carcinoma (HCC) and the potential role and mechanisms of IFITM3 in c-myc-mediated tumor proliferation remain unclear. In this study, we investigated a positive correlation between the expression of IFITM3 and c-myc in HCC. The down-regulation of IFITM3 significantly reduced c-myc expression and inhibited the proliferation of HCC in vitro and in vivo. In addition, upregulated c-myc expression restored the decrease in cell proliferation caused by the downregulation of IFITM3, while downregulation of c-myc reduced the proliferation of HCC enhanced by IFITM3. Mechanistically, IFITM3 regulates c-myc expression via the ERK1/2 signalling pathway. In conclusion, a novel path of IFITM3â€“ERK1/2â€“c-myc regulatory circuitry was identified, and its dysfunction may lead to HCC tumorigenesis.