MiR-17-5p promoter methylation regulated by DNA methyltransferase 3 beta (DNMT3B) expedites endometriosis via the Krüppel-like factor 12 (KLF12)/Wnt/ß-catenin axis.

Endometriosis (EM) is a common chronic disease in women with a high incidence, and aberrant DNA methylation and circulating endometrial cells (CECs) have been reported to be involved in the development of EM. However, the underlying mechanisms by which DNA methylation regulates EM progression have not been fully elucidated. In our study, we demonstrated that the DNA methyltransferase 3 beta (DNMT3B)-mediated DNA methylation modification enhanced EM progression through regulating miR-17-5p/KLF12/Wnt/ß-catenin axis. In detail, expression levels of miR-17-5p were significantly downregulated in EM tissues and serums, and we found that DNMT3B elevated the methylation modification of the miR-17-5p promoter, thereby suppressing the expression of miR-17-5p. Subsequently, functional experiments showed that silencing DNMT3B inhibited cell viability and epithelial-mesenchymal transition (EMT) and promoted cell apoptosis in CECs, whereas this effect could be reversed by knocking down miR-17-5p. Besides, overexpression of miR-17-5p repressed EM progression in vivo. Moreover, we found that miR-17-5p could target negative regulation of Krüppel-like factor 12 (KLF12) and KLF12 overexpression could rescue the effect of over-miR-17-5p. Besides, miR-17-5p was able to suppress the Wnt/ß-catenin signaling pathway, and blocked Wnt/ß-catenin pathway by XAV-939 reversed the influence of knockdown of miR-17-5p. Overall, our data indicated that DNMT3B-mediated DNA methylation leading to miR-17-5p inhibition exacerbated the process of EM by targeting KLF12/Wnt/ß-catenin axis, which provided a new perspective on targeted therapies for EM.

Verification a model of predicting vaginal birth after cesarean delivery in Chinese pregnant women.

The objective of our research was to confirm the prediction role of Grobman model for vaginal birth after cesarean (VBAC) in Chinese pregnant women. In this research, 535 pregnant who had once cesarean delivery and the least once subsequent try to a vaginal labor in Jiaxing of China were involved. The Grobman background factors and five new factors were included. Overall, in total of 456 women had successful VBAC, the success percent was 85.2%. The new background variable "maternal height" was considered as an additional predictor for VBAC. The Grobman model's area under the curve (AUC) was 0.811 (95% CI = 0.751-0.870) and the AUC of this modified model combined 2 new factors was 0.834 (95% CI = 0.781-0.886). Nevertheless, there has no markedly difference between these 2 models of the AUC. In conclusion, the Grobman model was suitable for Chinese pregnant. However, further improvements were needed to make a new predictive model of VBAC success rate for Chinese pregnant women through analyzing the clinical data of vaginal trial delivery after cesarean section.