miR-19a promotes cell growth and tumorigenesis through targeting SOCS1 in gastric cancer.

Accumulating evidence has shown that microRNAs are involved in cancer development and progression. However, it remains unknown about the potential role of miR-19a in the pathogenesis of gastric cancer. Here, we report that suppressor of cytokine signaling 1 (SOCS1) is a novel target of miR-19a in gastric cancer cells and that miR-19a expression is inversely correlated with SOCS1 expression in gastric cancer cells and a subset of gastric cancer tissues. Ectopic expression of miR-19a dramatically promoted proliferation and tumorigenicity of gastric cancer cells both in vitro and in vivo. Moreover, we showed that silencing of SOCS1 promoted cell growth and colony formation resembling that of miR-19a overexpression, whereas re-introduction of SOCS1 (without the 3'-UTR) attenuated the pro-tumorigenic functions. Taken together, our findings suggest that the SOCS1 gene is a direct target of miR-19a, which functions as an oncogenic miRNA in gastric cancer by repressing the expression of tumor suppressor SOCS1.

Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer.

Star-shaped polymer micelles have good stability against dilution with water, showing promising application in drug delivery. In this work, biodegradable micelles made from star-shaped poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer were prepared and used to deliver doxorubicin (Dox) in vitro and in vivo. First, an acrylated monomethoxy poly (ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) diblock copolymer was synthesized, which then self-assembled into micelles, with a core-shell structure, in water. Then, the double bonds at the end of the PCL blocks were conjugated together by radical polymerization, forming star-shaped MPEG-PCL (SSMPEG-PCL) micelles. These SSMPEG-PCL micelles were monodispersed (polydispersity index = 0.11), with mean diameter of ≈25 nm, in water. Blank SSMPEG-PCL micelles had little cytotoxicity and did not induce obvious hemolysis in vitro. The critical micelle concentration of the SSMPEG-PCL micelles was five times lower than that of the MPEG-PCL micelles. Dox was directly loaded into SSMPEG-PCL micelles by a pH-induced self-assembly method. Dox loading did not significantly affect the particle size of SSMPEG-PCL micelles. Dox-loaded SSMPEG-PCL (Dox/SSMPEG-PCL) micelles slowly released Dox in vitro, and the Dox release at pH 5.5 was faster than that at pH 7.0. Also, encapsulation of Dox in SSMPEG-PCL micelles enhanced the anticancer activity of Dox in vitro. Furthermore, the therapeutic efficiency of Dox/SSMPEG-PCL on colon cancer mouse model was evaluated. Dox/SSMPEG-PCL caused a more significant inhibitory effect on tumor growth than did free Dox or controls (P < 0.05), which indicated that Dox/SSMPEG-PCL had enhanced anticolon cancer activity in vivo. Analysis with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed that Dox/SSMPEG-PCL induced more tumor cell apoptosis than free Dox or controls. These results suggested that SSMPEG-PCL micelles have promising application in doxorubicin delivery for the enhancement of anticancer effect.

NAD(P)H quinone oxidoreductase 1 (NQO1) genetic C609T polymorphism is associated with the risk of digestive tract cancer: a meta-analysis based on 21 case-control studies.

The relationships between the NAD(P)H quinone oxidoreductase 1 (NQO1) C609T polymorphism and the risk of digestive tract (DT) cancer are controversial. Therefore, we performed a meta-analysis to assess the relationships. The databases of Medline, Embase, and WanFang (updated to 15 May 2011) were reviewed. Odds ratios and 95% confidence intervals were calculated to assess the strength of the associations. Overall, 21 individual case-control studies in 20 papers with 5340 cases and 5911 controls were included in this meta-analysis. The results of combined analyses indicated that the T allele of NQO1 C609T was significantly associated with increased risk of DT cancer [odds ratio (95% CI): 1.58 (1.22-2.07) for TT vs. CC and 1.13 (1.06-1.22) for T carriers vs. C carriers]. Subgroup analyses for different types of cancers indicated that the T allele was significantly associated with an increased risk of gastric cancer [1.19 (1.13-1.47) for T carriers vs. C carriers], but not with esophageal cancer [1.05 (0.86-1.27) for T carriers vs. C carriers] and colorectal cancer [1.09 (0.98-1.21) for T carriers vs. CC]. Subgroup analyses for ethnicities and countries indicated that the T allele was associated with risk of DT cancer among Europeans [1.52 (1.05-2.19) for TT vs. CC] and Asians [1.52 (1.05-2.19) for TT vs. CC], and German, Indian, and Chinese populations but not among English and Japanese populations. In addition, subgroup analyses also indicated that the T allele was significantly associated with risk of DT cancer in studies with large and small sample sizes and in population-based studies, but not in hospital-based studies. This meta-analysis suggests that NQO1 C609T is significantly associated with risk of DT cancer among both Europeans and Asians, especially gastric cancer. Because of the limited number of cases and controls in the subgroup analyses, more well-designed studies with a large sample of participants are needed to verify our findings.