TWIST is an important transcription factor during embryonic development and has recently been found to promote the epithelial-mesenchymal transition (EMT) phenomenon seen during the initial steps of tumor metastasis. To further investigate the potential targets and interacting genes of TWIST in human gastric cancer, we performed microarray analysis to compare the gene expression profiles in HGC-27 cells, with or without small interfering RNA (siRNA)-mediated depletion of TWIST. Our results showed that NF1, RAP1A, SRPX, RBL2, PFDN4, ILK, F2R, ERBB3, and MYB were up-regulated, whereas AKR1C2, FOS, GDF15, NR2F1, ATM, and CTPS were down-regulated after TWIST depletion. Moreover, TWIST-depleted HGC-27 cells showed a reversal of the morphologic and molecular changes associated with EMT. These results provide evidence that TWIST regulates the expression of several genes involved in the differentiation, adhesion, and proliferation of gastric cancer cells. The role of TWIST in the development of certain types of gastric cancer is discussed. Anat Rec, 292:262-270, 2009Rec, 292:262-270, . 2008 Wiley-Liss, Inc.Key words: TWIST; siRNA; epithelial-mesenchymal transition; gastric cancer; microarray Epithelial-mesenchymal transition (EMT) is pivotal for morphogenesis and in the transformation of early stage tumors into invasive malignancies (Kang and Massague, 2004). Cells undergoing EMT-characterized by the loss of cell polarity, cell-basement membrane adhesion, and cell-cell contacts-lose expression of epithelial markers (such as E-cadherin and catenin) and acquire expression of mesenchymal components (such as vimentin, fibronectin, and N-cadherin). Recent studies have shown that TWIST is one of the main regulatory proteins that promote EMT and the metastatic phenotype of cells (Karreth and Tuveson, 2004). Increased levels of TWIST are found in a wide range of cancers and are positively correlated with tumor aggressiveness and poor survival rates (Yang et al., 2004), suggesting a general role for TWIST in cancer development.TWIST is a basic helix-loop-helix (bHLH) transcription regulator that can form homodimers or heterodimers with partners that also contain an HLH domain. Depending on the protein partners in the dimers, these complexes play distinct roles in regulating the expression of downstream genes, acting either as activators or repressors. For example, TWIST homodimers can bind to the E-box of the E-cadherin promoter, repressing its expression, whereas their binding to the E-box of the Akt2 gene enhances its expression (Cheng et al

Background To determine the relation between daily glycemic fluturation and the intestinal mucosal barrier dysfunction in type 2 diabetes mellitus (T2DM). Methods Totally 66 patients with T2DM were enrolled, 33 healthy volunteers were also recruited according to the enrolled patients’ gender and age in a ratio of 2: 1. Patients were bisected by the median of endotoxins level into low(< 12.31 μ/l, n = 33) and high(≥12.31 μ/l, n = 33) blood endotoxin groups. Clinical data and blood glucose fluctuations were compared between groups. Multivariate regression analysis was used to determine the independent factors affecting the intestinal mucosal barrier. Results Serum endotoxin [12.1 (4.2~22.0) vs 3.2 (1.3~6.0), P < 0.001] and fasting blood glucose levels [9.8 ± 3.6 vs 5.4 ± 0.7, P < 0.001] were significantly higher in patients with T2DM than the control group. The standard deviation of blood glucose (SDBG) within 1 day [2.9 (2.0~3.3) vs. 2.1 (1.6~2.5), P = 0.012] and the largest amplitude of glycemic excursions (LAGE) [7.5 (5.4~8.9) vs. 5.9 (4.3~7.4), P = 0.034] were higher in the high endotoxin group than in the low endotoxin group. A multiple linear stepwise regression revealed a positive correlation between SDBG with endotoxin (standard partial regression coefficient = 0.255, P = 0.039). Conclusions T2DM patients who incapable of maintaining stable blood glucose level are at a higher risk to associated with intestinal mucosal barrier injury.

Abstract. Identifying the genetic variants that alter MUC1 protein expression may further our understanding of the risk for development of gastric cancer (GC). We used PCR-SSPs to identify the genotype of MUC1 A/G polymorphism at its 568 site of exon 2 and immunohistochemistry to detect MUC1 protein expression in GC patients and non-cancer subjects and analyzed the association between this polymorphism and MUC1 protein expression. We found that the frequency of AA genotype was significantly high in the GC patients and the risk for GC in AA genotype carriers increased 1.81-fold. Moreover, we found a significant underexpression of MUC1 protein in GC as compared to non-cancer subjects, which was negatively correlated to AA genotype of MUC1 (r=-0.1790, P=0.004). Furthermore, this study provides a possible mechanistic insight that the MUC1 A/G polymorphism at its 568 site disrupts the physiological functions of MUC1 which is important to the physiological protection of gastric mucosa. Thus we have provided evidence that may identify the MUC1 A/G polymorphism at 568 site, as a potential genetic factor which leads to an increase in susceptibility for GC through alteration of MUC1 gene and MUC1 expression in the population that carry the A allele.