Histone acetyltransferase GCN5 is a critical component of the TGF-β/Smad signaling pathway in breast cancer cells; however, it remains unknown whether it is involved in the development and progression of breast cancer. The present study investigated the role of GCN5 in the induction of the EMT by TGF-β1 in breast cancer cells and its underlying molecular mechanism of action. GCN5 activity was elevated and GCN5 mRNA expression and protein expression were increased in MDA-MB231 cells following stimulation with TGF-β1. Furthermore, TGF-β1 stimulation decreased expression of the epithelial cell marker E-cadherin and increased expression of the mesenchymal cell markers, N-cadherin and vimentin, as well as the expression of other EMT markers, including snail and slug. However, these changes were reversed following GCN5 knockdown leading to the downregulation of GCN5 expression. GCN5 knockdown also inhibited the viability, migration and invasion of MDA-MB231 cells, decreased the expression of p-STAT3, p-AKT, MMP9 and E2F1, and increased the expression of p21 in MDA-MB231 cells compared with cells stimulated with TGF-β1 alone. Therefore, GCN5 may work downstream of TGF-β/Smad signaling pathway to regulate the EMT in breast cancer.
Previous studies were controversial in the effects of metabolic syndrome (MetS) on semen quality and circulating sex hormones, and thus we conducted a systematic review and meta-analysis to clarify the association. A systematic search was conducted in public databases to identify all relevant studies, and study-specific standardized mean differences (SMD) and 95% confidence intervals (CI) were pooled using a random-effects model. Finally, 11 studies were identified with a total of 1,731 MetS cases and 11,740 controls. Compared with the controls, MetS cases had a statistically significant decrease of sperm total count (SMD: −0.96, 95% CI: −1.58 to −0.31), sperm concentration (SMD: −1.13, 95% CI: −1.85 to −0.41), sperm normal morphology (SMD: −0.61, 95% CI: −1.01 to −0.21), sperm progressive motility (SMD: −0.58, 95% CI: −1.00 to −0.17), sperm vitality (SMD: −0.83, 95% CI: −1.11 to −0.54), circulating follicle-stimulating hormone (SMD: −0.87, 95% CI: −1.53 to −0.21), testosterone (SMD: −5.61, 95% CI: −10.90 to −0.31), and inhibin B (SMD: −2.42, 95% CI: −4.52 to −0.32), and a statistically significant increase of sperm DNA fragmentation (SMD: 0.76, 95% CI: 0.45 to 1.06) and mitochondrial membrane potential (SMD: 0.89, 95% CI: 0.49 to 1.28). No significant difference was found in semen volume, sperm total motility, circulating luteinizing hormone (LH), estradiol, prolactin and anti-Müllerian hormone (AMH) (P > 0.05). In conclusion, this meta-analysis demonstrated the effects of MetS on almost all the semen parameters and part of the circulating sex hormones, and MetS tended to be a risk factor for male infertility. Further larger-scale prospective designed studies were needed to confirm our findings.
Iodine-131 (131I) is widely used for the treatment of thyroid-related diseases. This study aimed to investigate the expression of p53 and BTG2 genes following 131I therapy in thyroid cancer cell line SW579 and the possible underlying mechanism. SW579 human thyroid squamous carcinoma cells were cultured and treated with 131I. They were then assessed for 131I uptake, cell viability, apoptosis, cell cycle arrest, p53 expression, and BTG2 gene expression. SW579 cells were transfected with BTG2 siRNA, p53 siRNA and siNC and were then examined for the same aforementioned parameters. When treated with a JNK inhibitor of SP600125 and 131I or with a NF-κB inhibitor of BMS-345541 and 131I, non-transfected SW579 cells were assessed in JNK/NFκB pathways. It was observed that 131I significantly inhibited cell proliferation, promoted cell apoptosis and cell cycle arrest. Both BTG2 and p53 expression were enhanced in a dose-dependent manner. An increase in cell viability by up-regulation in Bcl2 gene, a decrease in apoptosis by enhanced CDK2 gene expression and a decrease in cell cycle arrest at G0/G1 phase were also observed in SW579 cell lines transfected with silenced BTG2 gene. When treated with SP600125 and 131I, the non-transfected SW579 cell lines significantly inhibited JNK pathway, NF-κB pathway and the expression of BTG2. However, when treated with BMS-345541 and 131I, only the NF-κB pathway was suppressed. 131I suppressed cell proliferation, induced cell apoptosis, and promoted cell cycle arrest of thyroid cancer cells by up-regulating B-cell translocation gene 2-mediated activation of JNK/NF-κB pathways.
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