MAPRE3 as an epigenetic target of EZH2 restricts ovarian cancer proliferation in vitro and in vivo.

Ovarian cancer (OC) is a lethal gynecologic cancer and the common cause of death within women worldwide. The polycomb group protein enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase highly expressed in various tumors, including OC. However, the mechanistic basis of EZH2 oncogenic activity in OC remain incompletely understood. Bioinformatics analysis showed that the expression of MAPRE3 was lower in OC tissues than in normal tissues, and was positively correlated with the overall survival. MAPRE3 overexpression decreased cell growth, inducing cell cycle arrest and apoptosis in OC cells, whereas MAPRE3 silencing promoted proliferation and accelerated cell cycle progression of OC cells. The in vivo study validated that overexpression of MAPRE3 impeded tumor formation and growth of OC xenografts in nude mice. In addition, knockdown of EZH2 in OC cells downregulated H3K27me3 expression and increased MAPRE3 expression. Inhibiting EZH2 in OC cells reduced the enrichment of H3K27me3 on the promoter of MAPRE3. Furthermore, MAPRE3 silencing significantly reversed changes in the expression of cell cycle and apoptosis-related markers and cell growth mediated by EZH2 knockdown in OC cells. MAPRE3 functions as a suppressor of OC and is epigenetic repressed by EZH2, suggesting a potential therapeutic strategy for OC by targeting EZH2/MAPRE3 axis.

Coeliac disease and postpartum depression: are they linked? A two-sample Mendelian randomization study.

Background: To explore the potential causal associations between coeliac disease(CD) and postpartum depression(PPD) by using two-sample Mendelian randomization(MR) analysis. Methods: The IEU OPEN GWAS project was utilized to identify genetic loci strongly associated with CD as instrumental variables (IVs), and MR analysis was performed using inverse variance weighting(IVW), weighted median, weighted model, and MR-Egger. MR analyses were used to examine whether there was a link between CD and PPD, with an OR and 95% CI. Meanwhile, the relationship between CD and depression(DP) was analyzed using MR. The sensitivity analysis was conducted using MR-Egger intercept analysis, Cochran's Q test, and leave-one-out analysis. Results: From the GWAS online database, 13 single-nucleotide polymorphisms (SNPs) were chosen as IVs. The IVW results showed a relationship between PPD and a genetically predicted risk of developing CD (OR = 1.022, 95% CI: 1.001-1.044, P = 0.043). However, the presence of DP was not linked with CD (OR=0.991, 95% CI: 0.978-1.003, P=0.151). Potential horizontal pleiotropy was not discovered using MR-Egger intercept analysis (PPD: P=0.725; DP: P=0.785), and Cochran's Q test for heterogeneity revealed no significant heterogeneity (PPD: P=0.486; DP: P=0.909). A leave-one-out analysis found that individual SNPs had minimal effect on overall causal estimations. Conclusion: MR research discovered a link between CD and PPD.