eIF3 regulates migration, invasion and apoptosis in cadmium transformed 16HBE cells and is a novel biomarker of cadmium exposure in a rat model and in workers

Abstract

Translation (eukaryotic) initiation factor 3 (eIF3 or TIF3) has been found to be a proto-oncogene in cadmium (Cd) response both in vitro and vivo, but whether eIF3 may serve as a biomarker of Cd exposure is still unclear. This study aimed to investigate whether eIF3 could serve as a novel biomarker of Cd toxicity in cells, animals and workers, and regulate the apoptosis, migration and invasion in human bronchial epithelial cell (16HBE cells) transformation with cadmium chloride (CdCl₂). In CdCl₂ transformed 16HBE cells, eIF3 expression increased gradually, and sequencing did not identify mutation and methylation of eIF3. In 16HBE cells with eIF3 silencing by siRNA and CdCl₂ treated 16HBE cells of the 15^th and 35^th generations, the apoptosis, migration and invasion were significantly inhibited, and the expressions of relevant genes were also altered (P < 0.05). In CdCl₂ treated rats, eIF3 mRNA expression increased to different extents in the blood, liver, kidney, heart and lung, and this increase was dependent on the Cd concentration (P < 0.05). The eIF3 mRNA expression was related to the mRNA expressions of AKT, BAX, BCL-2, E-CADHERIN, CASPASE-3, EGFR, FOXC2, STAT3, TGF-β1 and VIMENTIN (P < 0.05). In 181 workers with Cd exposure, the eIF3 mRNA expression was positively related to the blood Cd, urine Cd and β2-microglobulin content (P < 0.05). This study showed that abnormally expressed eIF3 may regulate the apoptosis, migration and invasion of 16HBE cells with Cd toxicity. This suggests that eIF3 may become a novel and valuable biomarker of Cd toxicity and Cd-induced effects, and may regulate apoptosis, migration and invasion of 16HBE cells. Thus, the detection of eIF3 expression is important for the monitoring of Cd toxicity in humans.