Molecular characterization, expression and functional analysis of yak IFITM3 gene.

IFITM3 is interferon-induced transmembrane 3, which plays an extremely key role in anti-proliferation, anti-virus and anti-tumor diseases. In this study, the yak (Bos grunniens) IFITM 3 (BgIFITM 3) gene contained a 5′-untranslated region (UTR) (25 bp), a coding region (441 bp), and a 3′-UTR (115 bp). The expression of BgIFITM 3 gene in liver was significantly higher than that in heart, spleen, lung and kidney (P < 0.01). BgIFITM3 protein was localized on the yak hepatocyte plasma membrane, and its expression was significantly different between 1 day and 15 months of age (P < 0.05). Moreover, the prokaryotic expression vector of BgIFITM3 protein was constructed and expressed successfully, with a molecular weight of 19.5 kDa. The activities of yak hepatocyte were significantly inhibited after treating with BgIFITM3 protein (10 and 20 μg/mL) (P < 0.01). The expression levels of ERBB -2, IRS -1, PI 3 KR -1, AKT -1 and MAPK -3 were significantly lower after treating with 20 μg/mL BgIFITM3 protein (P < 0.05). Besides, the activities of HepG2 cells were significantly inhibited after treating with BgIFITM3 protein (1, 10 and 20 μg/mL) (P < 0.05). While, the cloning ability and migration ability of HepG2 cells were significantly inhibited after treating with 10 μg/mL BgIFITM3 protein (P < 0.05). Finally, the mitochondria of HepG2 cells was concentrated, cristae widened, and the double film density of mitochondria was increased after treating with 10 μg/mL BgIFITM3 protein. After 10 μg/mL BgIFITM3 protein treating, the expression levels of VDAC -2, VDAC -3 and p 53 genes were significantly increased, but the expression level of GPX -4 gene was significantly decreased (P < 0.01). Taken together, the BgIFITM3 protein could inhibit the proliferations of yak hepatocyte and HepG2 cells by regulating the PI3K/Akt pathway or ferroptosis-related genes, respectively. These results benefit for further study of the function of BgIFITM3 protein. [ABSTRACT FROM AUTHOR]