Basic Transcription Factor 3 Is Required for Proliferation and Epithelial-Mesenchymal Transition via Regulation of FOXM1 and JAK2/STAT3 Signaling in Gastric Cancer.

Gastric cancer (GC) is the most common epithelial malignancy worldwide. Basic transcription factor 3 (BTF3) plays a crucial role in the regulation of various biological processes. We designed experiments to investigate the molecular mechanism underlying the role of BTF3 in GC cell proliferation and metastasis. We confirmed that BTF3 expression was decreased in GC tissues and several GC cell lines. Lentivirus-mediated downregulation of BTF3 reduced cell proliferation, induced S and G2/M cell cycle arrest, and increased apoptosis. Knockdown of BTF3 significantly reduced the expression of Forkhead box M1 (FOXM1). Upregulation of FOXM1 significantly inhibited the decrease in cell proliferation due to BTF3 silencing, S and G2/M cell cycle arrest, and increase in apoptosis. Knockdown of BTF3 decreased Ki-67 and PCNA expression, whereas it increased p27 expression, which was inhibited by upregulation of FOXM1. Knockdown of BTF3 significantly decreased the ability to invade and migrate. Moreover, knockdown of BTF3 increased E-cadherin expression, whereas it decreased N-cadherin and ZEB2 expression, indicating a decrease in epithelial-mesenchymal transition (EMT). Phosphorylation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) was significantly inhibited by knockdown of BTF3. IL-6-stimulated phosphorylation of STAT3 and JAK2 markedly suppressed inhibition of EMT due to BTF3 silencing. Silencing of BTF3 decreased tumor volume and weight and reduced peritoneal nodules in implanted tumors. Our findings provide a novel understanding of the mechanism of GC and highlight the important role of BTF3/FOXM1 in tumor growth and BTF3/JAK2/STAT3 in EMT and metastasis.

Prognostic significance of ischemia-modified albumin for severe acute pancreatitis.

Background: Severe acute pancreatitis (SAP) is characterized by the noxious combination of severe systemic inflammation and hypoperfusion and oxidative stress. Ischemia-modified albumin (IMA) was recognized as a novel marker of oxidative stress and ischemia. The purpose of this study was to evaluate serum IMA level in patients with SAP and analyze its prognostic significance. Methods: A total of 72 patients with SAP were enrolled. Serum IMA level was measured within 24 hours of the onset of SAP, and baseline characteristics were recorded. The BISAP, APACHE II and SOFA scores were calculated. Multivariate logistic regression and receiver operating characteristic curve analyses were used to evaluate predictive ability of LMA for in-hospital mortality of SAP. Kaplan-Meier analysis was further used to compare in-hospital mortality difference between high LMA and low LMA. Results: The overall in-hospital mortality rate of all 72 SAP patients was 23.6%. Non-survivor group had higher serum IMA (107.2±10.8 VS 88.4±11.9, P<0.05) than survivor group. Otherwise, the optimal cutoff levels for the IMA predicting in-hospital mortality of patients with SAP was 112 U/ml using a sensitivity of 77.4% and a specificity of 76.2% as optimal conditions (AUC, 0.734; 95% CI: 0.615-0.852; P=0.002). IMA level also was confirmed as an independent prognostic factor for SAP in multivariate analysis. Patient with high IMA level (≥112 U/ml) had poorer survival rate than low IMA (<112 U/ml) in log-rank test of Kaplan-Meier survival analysis (P<0.05). Conclusions: Serum IMA level can be considered as an independent predictor for in-hospital mortality of patients with SAP.