MYC inhibits migration of lung cancer cell lines by down-regulating AKR1C1 expression

Objective To explore the role of MYC in lung cancer cell migration and reveal the mechanism affecting migration. Methods siRNA MYC or pRK5-MYC plasmid was transfected into lung cancer cells A549. Cell migration was examined by wound healing assay. The mRNA expression of candidate genes AKR1C1 and AKR1C3 was detected by fluorescence quantitative PCR. Dual luciferase reporting assay and chromatin immunoprecipitation assay (ChIP) verified the transcriptional regulation of target genes by MYC. A549 cells were transfected with MYC and AKR1C1 siRNA or pRK5-MYC and pRK5-AKR1C1 at the same time. Wound healing assay and Transwell were used to examine cell migration and cell invasion respectively. Results Knockdown MYC in A549 cells promoted cell migration, and over-expression of MYC inhibited cell migration. The level of protein and mRNA of AKR1C1 was significantly increased(P＜0.01) after knockdown MYC. The ChIP assay showed that MYC binded to the response element (RE) of AKR1C1. Compared with control plasmids, MYC induced the expression of luciferase in RE-containing plasmids. Decreased expression of AKR1C1 inhibited the invasion and migration of lung cancer cells(P＜0.05). AKR1C1 reduced cell invasion and migration caused by MYC loss(P＜0.05). Conclusions MYC might inhibit cancer cell migration by inhibiting AKR1C1 expression.