Confirmation of a metastasis-specific microRNA signature in primary colon cancer

The identification of patients with high-risk stage II colon cancer who may benefit from adjuvant therapy may allow the clinical approach to be tailored for these patients based on an understanding of tumour biology. MicroRNAs have been proposed as markers of the prognosis or treatment response in colorectal cancer. Recently, a 2-microRNA signature (l et-7i and miR-10b) was proposed to identify colorectal cancer patients at risk of developing distant metastasis. We assessed the prognostic value of this signature and additional candidate microRNAs in an independent, clinically well-defined, prospectively collected cohort of primary colon cancer patients including stage I-II colon cancer without and stage III colon cancer with adjuvant treatment. The 2-microRNA signature specifically predicted hepatic recurrence in the stage I-II group, but not the overall ability to develop distant metastasis. The addition of miR-30b to the 2-microRNA signature allowed the prediction of both distant metastasis and hepatic recurrence in patients with stage I-II colon cancer who did not receive adjuvant chemotherapy. Available gene expression data allowed us to associate m iR-30b expression with axon guidance and l et-7i expression with cell adhesion, migration, and motility

Effects of GCK, GCKR, G6PC2 and MTNR1B Variants on Glucose Metabolism and Insulin Secretion

were found to modulate the fasting glucose levels. The current study aimed to replicate this association in the Chinese population and further analyze their effects on biphasic insulin secretion.). genetic variant was associated with first-phase insulin secretion, but not second-phase insulin secretion

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Greenness surrounding schools and visual impairment in Chinese children and adolescents

Background: Evidence concerning the effects of greenness on childhood visual impairment is scarce. Objectives: We aimed to assess whether greenness surrounding schools was associated with visual impairment prevalence and visual acuity levels in Chinese schoolchildren and whether the associations might be explained by reduced air pollution. Methods: In September 2013, we recruited 61,995 children and adolescents 6-18 years of age from 94 schools in seven provinces/municipalities in China. Greenness exposure was assessed using the normalized difference vegetation index (NDVI) and the soil-adjusted vegetation index (SAVI) from July to August 2013. Visual impairment was defined as at least one visual acuity level (dimensionless) lower than 4.9 (Snellen 5/6 equivalent). Three-year annual averages of particulate matter (PM) with an aerodynamic diameter of ≤1μm (PM1) and nitrogen dioxide (NO2) at each school were assessed using machine learning methods. We used generalized linear mixed models to estimate the associations between greenness and prevalent visual impairment and visual acuity levels and used mediation analyses to explore the potential mediating role of air pollution. Results: In the adjusted model, an interquartile range increase in NDVI500m was associated with lower odds of prevalent visual impairment [odds ratio (OR)=0.95; 95% confidence interval (CI): 0.93, 0.97]. The same increase in NDVI500m was also associated with 0.012 (95% CI: 0.008, 0.015) and 0.011 (95% CI: 0.007, 0.015) increases in visual acuity levels for left- and right-eye, respectively. Our results also suggested that PM1 and NO2 significantly mediated the association between NDVI500m and visual impairment. Similar effect estimates were observed for SAVI500m, and our estimates were generally robust in several sensitivity analyses. Discussion: These findings suggest higher greenness surrounding schools might reduce the risk of visual impairment, possibly owing in part to lower PM1 and NO2 in vegetated areas. Further longitudinal studies with more precise greenness assessment are warranted to confirm these findings

FOXP3 promotes tumor growth and metastasis by activating Wnt/β-catenin signaling pathway and EMT in non-small cell lung cancer

Abstract Background The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). Methods One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results. Results NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial–mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/β-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with β-catenin and TCF4 to enhance the functions of β-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction. Conclusions FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC