The polycomb group protein EZH2 induces epithelial–mesenchymal transition and pluripotent phenotype of gastric cancer cells by binding to PTEN promoter

Abstract Background The influences of oncogenic Ezh2 on the progression and prognosis of gastric cancer (GC) and the underlying mechanisms are still poorly understood. Here, we aimed at investigating clinicopathological significance of Ezh2 in GC and the mechanisms underlying its function in GC development. Methods The expression level of Ezh2 was determined by qRT-PCR, immunoblot, and immunohistochemistry analysis in 156 pairs of GC tissues and adjacent normal gastric mucosa tissues. The biological functions of Ezh2 were assessed by in vitro and in vivo functional experiments. Chromatin immunoprecipitation (ChIP), luciferase, and Western blotting analyses were utilized to identify the relationship between Ezh2 and the PTEN/Akt signaling. Results The expression of Ezh2 was higher in gastric cancer tissues in comparison with para-nontumorous epithelium. High expression of Ezh2 was associated with more aggressive biological behavior and poor prognosis in GC. In vitro studies indicated that Ezh2 promoted GC cells’ proliferation and clonogenicity. Besides, Ezh2 led to the acquisition of epithelial–mesenchymal transition (EMT) phenotype of GC cells and enhanced GC cell migration and invasion capacity. In particular, Ezh2 strengthened sphere-forming capacity of GC cells, indicating its role in the enrichment of GC stem cells. Furthermore, we found that PTEN/Akt signaling contributed to the effects of Ezh2 on cancer stem cells (CSC) and EMT phenotype in GC cells, and blocking PTEN signaling significantly rescued the effects of Ezh2. Conclusions Taken together, Ezh2 has a central role in regulating diverse aspects of the pathogenesis of GC in part by involving PTEN/Akt signaling, indicating that it could be an independent prognostic factor and potential therapeutic target

Association between low ambient temperature during pregnancy and adverse birth outcomes: A systematic review and meta-analysis

Abstract. Background:. Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein. Methods:. Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis. Results:. A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04–1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03–1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99–5.38). Conclusions:. Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors. Registration:. No. CRD42021259776 at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/)

Additional file 6:Table S3. of Bmi-1 regulates stem cell-like properties of gastric cancer cells via modulating miRNAs

Frequencies of altered expression of Bmi-1,miR-21 and miR-34a in the 74 gastric cancer tissues. (XLS 14 kb

Additional file 5: Table S2. of Bmi-1 regulates stem cell-like properties of gastric cancer cells via modulating miRNAs

The correlation between Bmi-1 and stem cell markers in gastric cancer tissues. (XLS 14 kb

Additional file 3: Figure S2. of Bmi-1 regulates stem cell-like properties of gastric cancer cells via modulating miRNAs

Representative figures of Bmi-1 and several CSC-related proteins in gastric tumors, its surrounding normal tissues, and paired metastatic cancer samples. (DOC 6222 kb

Additional file 1: of The polycomb group protein EZH2 induces epithelial–mesenchymal transition and pluripotent phenotype of gastric cancer cells by binding to PTEN promoter

Materials and Methods. Table S1. Relationship between EZH2 expression and clinicopathologic parameters of gastric cancer patients. Table S2. Univariate and multivariate analysis of clinicopathological factors for disease-free survival in gastric cancer (qRT-PCR cohort). Table S3. Univariate and multivariate analysis of clinicopathological factors for overall survival in gastric cancer (qRT-PCR cohort). Table S4. Univariate and multivariate analysis of clinicopathological factors for overall survival in gastric cancer (IHC cohort). Table S5. Correlation analysis of expression of stem cell related factors with EZH2. Table S6. Primers and siRNA sequences used in this study. (DOCX 67 kb