Methylation of ESR1 promoter induced by SNAI2-DNMT3B complex promotes epithelial-mesenchymal transition and correlates with poor prognosis in ERα-positive breast cancers.

Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα-negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc-finger transcriptional factor, recruited lysine-specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα-positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα-positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression-induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse-free survival and overall survival in ERα-positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial-mesenchymal transition in BC.

[Clinical significance of venous return disturbance in patients with osteonecrosis of femoral head].

OBJECTIVE: To evaluate the correlation of venous return disturbance (VRD), bone marrow edema (BME) and the amount of joint fluid with clinical symptoms in osteonecrosis of the femoral head (ONFH). METHODS: Twenty patients (25 hips) with ONFH proved by pathology were parallelly examined by 1.5 T MR and medullograph. RESULT: In total 25 hips VRD was observed in 16 hips with medullograph and 13 hips with the clinical symptoms (P <0.05). BME was found in 17 with MRI (P <0.01), and the was found in 15 hips with MRI (Spearman=0.949). VRD were found in 16 hydrarthrus. CONCLUSION: ONFH patients with clinical symptoms have VRD, BME and the hydrarthrus. The medullograph is of value in monitoring the development of ONFH.