MDIG promotes cisplatin resistance of lung adenocarcinoma by regulating ABC transporter expression via activation of the WNT/β-catenin signaling pathway

Mineral dust-induced gene (MDIG) is a proto- oncogene associated with lung cancer that serves a key role in the biological processes of tumorigenesis. The aim of the present study was to determine whether MDIG is involved in cisplatin (DDP) resistance in lung adenocarcinoma, and to investigate the associated molecular mechanism. In the present study, MDIG-knockdown and MDIG-overexpressing A549 cells and DDP-resistant A549/DDP cells were initially constructed, and then the mRNA and protein expression levels of MDIG and ATP-binding cassette (ABC) transporters (ABCB1, ABCC1, ABCG2), and the expression levels of the major associated proteins in the WNT/beta-catenin pathway were determined by reverse transcription-quantitative PCR and Western blotting experiments. The results revealed that the mRNA and protein expression levels of MDIG in A549/DDP cells were significantly higher compared with those in A549 cells, and that the protein expression levels of MDIG increased in a dose-dependent manner with increasing DDP concentrations. Overexpression of MDIG in A549 and A549/DDP cells led to an increase in the IC50 value, whereas silencing of MDIG led to a clear reduction in the IC50 value. The overexpression of MDIG in the A549 and A549/DDP cells markedly upregulated the mRNA and protein expression levels of ABCB1, ABCC1, ABCG2, WNT family member 5A, WNT family member 3A and active beta-catenin, and these were markedly decreased following MDIG silencing. Taken together, these results demonstrated that the DDP resistance of lung adenocarcinoma may be associated with an upregulation of MDIG expression, and that the expression levels of MDIG are positively associated with the degree of DDP resistance. Furthermore, MDIG promoted the expression of ABC transporters in tumor cells by activating the WNT/beta-catenin signaling pathway, which may, in turn, lead to DDP resistance in lung adenocarcinoma.