ABSTRACT
Human Dachshund homolog 1 (DACH1) is usually defined as a tumor suppressor, which plays an influential role in tumor growth and metastasis in a variety of cancer cells. However, the underlying mechanisms in these process are not yet fully clarified. In this study, DACH1 inhibited the invasion and metastasis of breast cancer cells by decreasing MMP9 expression. Mechanistically, DACH1 represses the transcriptional level of MMP9 by interacting with p65 and c-Jun at the NF-κB and AP-1 binding sites in MMP9 promoter respectively, and the association of DACH1 and p65 promote the recruitment of HDAC1 to the NF-κB binding site in MMP9 promoter, resulting in the reduction of the acetylation level and the transcriptional activity of p65. Accordingly, the level of MMP9 was decreased. In conclusion, we found a new mechanism that DACH1 could inhibit the metastasis of breast cancer cells by inhibiting the expression of MMP9.
ABSTRACT
BACKGROUND: Tumor necrosis factor superfamily member 4 (TNFSF4) has significant role in modulating autoimmune diseases (ADs) and single nucleotide polymorphism (SNP) is also related with the susceptibility to some diseases. So a meta-analysis aimed at systematically assessing the associations between TNFSF4 polymorphisms (rs2205960 G > A, rs704840 T > G and rs844648 G > A) and ADs risk was performed in Asians. METHODS: Total 14 eligible articles published before March 2019 involving 35 studies, of which 21 studies (16,109 cases and 26,378 controls) for rs2205960 G > A, 8 studies (2,424 cases and 3,692 controls) for rs704840 T > G, and 6 studies (3,839 cases and 5,867 controls) for rs844648 G > A were included. Effects of the three respective polymorphisms on the susceptibility to ADs were estimated by pooling the odds ratios (ORs) with their corresponding 95% confidence interval (95% CI) in allelic, dominant, recessive, heterozygous and homozygous models. RESULTS: The overall analysis revealed that all the rs2205960 G > A, rs704840 T > G and rs844648 G > A polymorphisms could increase the risk of ADs in allelic, dominant, recessive, heterozygous and homozygous models. Furthermore, subgroup analysis showed that both rs2205960 G > A and rs704840 T > G were significantly associated with the susceptibility to systemic lupus erythematosus (SLE). What's more, statistically significant association between rs2205960 G > A polymorphism and primary Sjögren's syndrome (pSS) susceptibility was also observed in allelic, dominant and heterozygous models. CONCLUSIONS: This current meta-analysis suggested that all of the three TNFSF4 polymorphisms may be associated with ADs susceptibility in Asians.