No abstract

An increasing body of evidence indicates that miR-149 can both suppress and promote tumor growth depending on the tumor type. However, the role of miR-149 in the progression of gastric cancer (GC) remains unknown. Here we report that miR-149 is a tumor suppressor in human gastric cancer. miR-149 expression is decreased in GC cell lines and clinical specimens in comparison to normal gastric epithelial cell and tissues, respectively. The expression levels of miR-149 also correlate with the differentiation degree of GC cells and tissues. Moreover, ectopic expression of miR-149 in gastric cancer cells inhibits proliferation and cell cycle progression by down-regulating ZBTB2, a potent repressor of the ARF-HDM2-p53-p21 pathway, with a potential binding site for miR-149 in its mRNA's 3′UTR. It is also found that ZBTB2 expression increases in GC cells and tissues compared to normal gastric epithelial cell and tissues, respectively. Silencing of ZBTB2 leads to suppression of cell growth and cell cycle arrest in G0/G1 phase, indicating that ZBTB2 may act as an oncogene in GC. Furthermore, transfection of miR-149 mimics into gastric cancer cells induces down-regulation of ZBTB2 and HDM2, and up-regulation of ARF, p53, and p21 compared to the controls. In summary, our data suggest that miR-149 functions as a tumor suppressor in human gastric cancer by, at least partially through, targeting ZBTB2.

We evaluated whole body and regional adipose tissue lipid kinetics and norepinephrine (NE) spillover during brief fasting in six lean [body mass index (BMI) 21 ± 1 kg/m2] and six upper-body obese (UBO; BMI 36 ± 1 kg/m2) women. At 14 h of fasting, abdominal adipose tissue glycerol and free fatty acid (FFA) release rates were lower ( P = 0.07), but whole body glycerol and FFA rates of appearance (Ra) were greater ( P < 0.05) in obese than in lean subjects. At 22 h of fasting, glycerol and FFA Ra increased less in obese (19.8 ± 7.0 and 87.1 ± 30.3 μmol/min, respectively) than in lean (44.2 ± 6.6 and 137.4 ± 30.4 μmol/min, respectively; P < 0.05) women. The percent increase in glycerol Ra correlated closely with the percent decline in plasma insulin in both groups ( r 2 = 0.85; P < 0.05). Whole body NE spillover declined in lean ( P < 0.05) but not obese subjects with continued fasting, whereas regional adipose tissue NE spillover did not change in either group. We conclude that, compared with lean women, in UBO women 1) basal adipose tissue lipolysis is lower, but whole body lipid kinetics is higher because of their greater fat mass; 2) the increase in lipolysis during fasting is blunted because of an attenuated decline in circulating insulin; and 3) downregulation of whole body sympathetic nervous system activity is impaired during fasting.