Exploring the external exposome using wearable passive samplers - The China BAPE study.

Environmental exposures are one of the greatest threats to human health, yet we lack tools to answer simple questions about our exposures: what are our personal exposure profiles and how do they change overtime (external exposome), how toxic are these chemicals, and what are the sources of these exposures? To capture variation in personal exposures to airborne chemicals in the gas and particulate phases and identify exposures which pose the greatest health risk, wearable exposure monitors can be deployed. In this study, we deployed passive air sampler wristbands with 84 healthy participants (aged 60-69 years) as part of the Biomarkers for Air Pollutants Exposure (China BAPE) study. Participants wore the wristband samplers for 3 days each month for five consecutive months. Passive samplers were analyzed using a novel gas chromatography high resolution mass spectrometry data-processing workflow to overcome the bottleneck of processing large datasets and improve confidence in the resulting identified features. The toxicity of chemicals observed frequently in personal exposures were predicted to identify exposures of potential concern via inhalation route or other routes of airborne contaminant exposure. Three exposures were highlighted based on elevated toxicity: dichlorvos from insecticides (mosquito/malaria control), naphthalene partly from mothballs, and 183 polyaromatic hydrocarbons from multiple sources. Other exposures explored in this study are linked to diet and personal care products, cigarette smoke, sunscreen, and antimicrobial soaps. We highlight the potential for this workflow employing wearable passive samplers for prioritizing chemicals of concern at both the community and individual level, and characterizing sources of exposures for follow up interventions.

Autophagy-related long non-coding RNA signature for ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) affects nearly 22,000 women annually in the United States and ranks fifth in cancer deaths, largely because of being diagnosed at an advanced stage. Autophagy is the cellular process of self-degrading damaged or degenerate proteins and organelles. Long non-coding RNAs (lncRNAs) are a group of RNA molecules whose transcripts are greater than 200 nt but are not translated into proteins. However, just a small number of autophagy-related lncRNAs have been explored in depth. METHODS: We used RNA sequencing data from The Cancer Genome Atlas (TCGA) and autophagy datasets to identify dysfunctional autophagy-related lncRNAs and provide potential useful biomarkers for OC diagnosis and prognosis. RESULTS: Seventeen differentially expressed lncRNAs (AC010186.3, AC006001.2, LBX2-AS1, SNHG17, AC011445.1, AC083880.1, MIR193BHG, AC025259.3, HCG14, AC007114.1, AC108673.2, USP30-AS1, AC010336.5, LINC01132, AC006333.2, LINC00665 and AC027348.1) were selected as independent prognostic factors for OC patients. Functional annotation of the data was performed through gene set enrichment analysis (GSEA). The results suggested that the high-risk group was mainly enriched in specific tumor-related and metabolism pathways. CONCLUSION: Based on the online databases, we identified novel autophagy-related lncRNAs for the prognosis of ovarian cancer.

Characterization of bone aluminum, a potential biomarker of cumulative exposure, within an occupational population from Zunyi, China.

OBJECTIVES: Aluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs). METHODS: We completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al. RESULTS: Median (interquartile range (IQR)) Al measurements were: 15 µg/g dry bone (IQR = 28) for bone Al; 34.9 µg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (ß = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (ß = 0.98, 95% CI: -0.14, 2.1; ß = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant. CONCLUSIONS: Bone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing.

Monitoring and assessment of formaldehyde levels in residential areas from two cities in Romania.

Formaldehyde has become a ubiquitous contaminant in the air, and people are exposed to it worldwide. However, few studies have evaluated the temporal-spatial levels/changes of formaldehyde exposure at residences, and the relationship between its outdoor and indoor levels has been rarely examined. The aim of this study was to assess community formaldehyde exposure in Sebes and Aiud, Romania to identify: (1) home environment characteristics that may play an important role in exposure; and understand: (2) if there were differences in formaldehyde levels between the two cities; (3) if there were temporal variations within each city; and (4) whether outdoor formaldehyde levels influence indoor levels. We simultaneously performed indoor and outdoor active air sampling for formaldehyde at each investigated residential location over a 3-year period and analyzed the samples by gas chromatography with flame ionization detector (GC-FID). The mean values of indoor and outdoor formaldehyde levels in both cities fell in the range 0.014-0.035 mg/m3. The correlation analysis indicated mostly positive but not significant (p > 0.05) correlations between indoor formaldehyde and microclimate factors (temperature, humidity, pressure). Notably, home insulation was found to be significantly correlated with increased indoor formaldehyde levels. There were no significant differences in mean indoor or outdoor formaldehyde levels between Sebes and Aiud over the 3-year study period. When comparing the formaldehyde levels in both cities over the 3-year period, only outdoor formaldehyde levels were significantly higher in 2016, as compared to those in 2017 and 2018.

Erratum: Phosphodiesterase-5 inhibition suppresses colonic inflammation-induced tumorigenesis via blocking the recruitment of MDSC.

[This corrects the article on p. 41 in vol. 7, PMID: 28123846.].

Peroral endoscopic myotomy is safe and effective in achalasia patients aged older than 60 years compared with younger patients.

AIM: Peroral endoscopic myotomy (POEM) has been proven to be effective for treating achalasia, but there are limited data on POEM in elderly patients. We therefore aimed to assess the role of POEM for achalasia in patients aged ≥60 years. METHODS: All consecutive patients that underwent POEM between December 2011 and November 2015 at a single center were retrospectively reviewed. Patients aged ≥60 years were assigned to group A, whereas patients aged <60 years were assigned to group B. Demographic data, clinical data and treatment outcomes were compared between the two groups. RESULTS: During the study period, 113 patients (18 in group A, and 95 in group B) were enrolled. The mean age of patients in group A was 63 ± 3.9 years (range 60-74 years; 55.6% women), and that for patients in group B was 37.7 ± 11.6 years (range 18-59 years; 42.2% women). The procedural time in group A was similar to group B (66.3 ± 33.3 vs 59.8 ± 24.2 min, P = 0.332). There were also no significant differences in the incidence of intraoperative complications (P = 1.000) and gastroesophageal reflux rate (P = 0.906) between the two groups. During the mean follow-up period of 25.2 months, treatment success (Eckardt score ≤3) was achieved in 92.9% of patients in group A, and 89.9% in group B (P = 1.000). CONCLUSIONS: As well as in younger patients, POEM can be safely carried out in elderly patients, providing significant symptom relief. POEM might be recommended as the first therapeutic approach to elderly achalasia patients. Geriatr Gerontol Int 2017; 17: 2407-2413.

Endoscopic submucosal tunnel dissection of upper gastrointestinal submucosal tumors: A comparative study of hook knife vs hybrid knife.

AIM: To compare the efficacy and safety of a hook knife (HO) with a hybrid knife (HK) during endoscopic submucosal tunnel dissection (ESTD) procedure. METHODS: Between August 2012 and December 2015, the ESTD procedure was performed for 83 upper GI submucosal lesions, which originated from the muscularis propria layer identified by upper endoscopy and endoscopic ultrasonography. Of these, 34 lesions were treated by a HO, whereas 49 lesions were treated by a HK. Data regarding age, gender, presenting symptoms, tumor location and size, procedure time, complications, en bloc resection rate and others were analyzed and compared between the two groups. RESULTS: There were no significant differences in the age, gender, presenting symptoms and tumor location between the two groups. ESTD was successfully completed in all the patients, and no case was converted to laparoscopy. The mean procedure time was significantly shorter in the HK group than in the HO group (41.3 ± 20.3 min vs 57.2 ± 28.0 min, P = 0.004). The mean frequency of device exchange was 1.4 ± 0.6 in the HK group and significantly less than 3.3 ± 0.6 in the HO group (P < 0.001). The differences in tumor size and histopathological diagnoses were not significant between the two groups (P = 0.813, P = 0.363, respectively). Both groups had an equal en bloc resection rate and complete resection rate. Additionally, the complication rate was similar between the two groups (P = 0.901). During the follow-up, no recurrence occurred in either group. CONCLUSION: We demonstrate for the first time that HO and HK do not differ in efficacy or safety, but HK reduces the frequency of device exchange and procedure time.

Endoscopic Submucosal Tunnel Dissection for Upper Gastrointestinal Submucosal Tumors Originating from the Muscularis Propria Layer: A Single-Center Study.

BACKGROUND/AIMS: In recent years, endoscopic submucosal tunnel dissection (ESTD) has gained popularity worldwide. The aim of this study was to evaluate the safety and efficacy of ESTD in treating upper gastrointestinal submucosal tumors (SMTs) in a large-volume endoscopic center. METHODS: Patients with SMTs were enrolled in this study between January 2012 and January 2015. Demographic data, clinical data, and treatment outcome were collected and analyzed. RESULTS: Seventy SMTs originating from the muscularis propria (MP) layer were identified in 69 patients. All patients successfully underwent the ESTD procedure. The mean procedure time was 49.0±29.5 minutes, and the mean tumor size was 18.7±7.2 mm. Among all lesions, the majority (70.0%) were located in the esophagus, 12.9% in the cardia, and 17.1% in the stomach. Complete resection was achieved in 67 lesions (95.7%). Perforation occurred in three patients (4.3%), who were treated by endoclips. Pneumothorax occurred in two patients (2.9%) and was successfully managed by thoracic drainage. During a median follow-up of 18.1 months, patients were free of local recurrence or distant metastasis. CONCLUSIONS: Our results demonstrated the feasibility and safety of ESTD in treating upper gastrointestinal SMTs originating from the MP layer. Large-scale comparative studies with other treatment methods should be conducted in the future.

Phosphodiesterase-5 inhibition suppresses colonic inflammation-induced tumorigenesis via blocking the recruitment of MDSC.

Phosphodiesterase 5 (PDE-5) is a major isoform of cGMP phosphodiesterase in diverse tissues and plays a critical role in regulating intracellular cGMP concentrations. However, the distribution and expression of PDE-5 in colitis-related colon cancer was still unclear, not even the function and mechanism. Western blotting and ELISA were performed to detect colonic PDE-5 expression in AOM/DSS-induced tumorigenesis model. Sildenafil, a specific PDE-5 inhibitor, was used to treat AOM/DSS-induced and AOM-induced colonic tumorigenesis model and DSS-induced colitis model. The leukocyte infiltration in colonic tissue was examined by flow cytometry and immunofluorescence staining. Further matrigel-based invasion assay was employed to determine the effects of Sildenafil on myeloid-derived suppressor cell (MDSC) in vitro. We first demonstrated the upregulation of colonic PDE-5 expression and the prevention role of PDE-5 inhibition in AOM/DSS-induced tumorigenesis model. More importantly, PDE-5 inhibitor Sildenafil inhibited colonic tumorigenesis dependent on inflammation and suppressed DSS-induced colitis. Molecular mechanism investigation indicated that Sildenafil regulated inflammation microenvironment via directly inhibiting MDSC infiltration in colonic tissue. The study provides solid evidence for the use of PDE-5 inhibitor in preventing and treating colonic inflammation-related tumorigenesis.

Accuracy of Magnetically Controlled Capsule Endoscopy, Compared With Conventional Gastroscopy, in Detection of Gastric Diseases.

BACKGROUND & AIMS: Diseases of the stomach, including gastric cancer and peptic ulcer, are the most common digestive diseases. It is impossible to visualize the entire stomach with the passive capsule currently used in practice because of the large size of the gastric cavity. A magnetically controlled capsule endoscopy (MCE) system has been designed to explore the stomach. We performed a prospective study to compare the accuracy of detection of gastric focal lesions by MCE vs conventional gastroscopy (the standard method). METHODS: We performed a multicenter blinded study comparing MCE with conventional gastroscopy in 350 patients (mean age, 46.6 y), with upper abdominal complaints scheduled to undergo gastroscopy at a tertiary center in China from August 2014 through December 2014. All patients underwent MCE, followed by conventional gastroscopy 2 hours later, without sedation. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of detection of gastric focal lesions by MCE, using gastroscopy as the standard. RESULTS: MCE detected gastric focal lesions in the whole stomach with 90.4% sensitivity (95% confidence interval [CI], 84.7%-96.1%), 94.7% specificity (95% CI, 91.9%-97.5%), a positive predictive value of 87.9% (95% CI, 81.7%-94.0%), a negative predictive value of 95.9% (95% CI, 93.4%-98.4%), and 93.4% accuracy (95% CI, 90.83%-96.02%). MCE detected focal lesions in the upper stomach (cardia, fundus, and body) with 90.2% sensitivity (95% CI, 82.0%-98.4%) and 96.7% specificity (95% CI, 94.4%-98.9%). MCE detected focal lesions in the lower stomach (angulus, antrum, and pylorus) with 90.6% sensitivity (95% CI, 82.7%-98.4%) and 97.9% specificity (95% CI, 96.1%-99.7%). MCE detected 1 advanced gastric carcinoma, 2 malignant lymphomas, and 1 early stage gastric tumor. MCE did not miss any lesions of significance (including tumors or large ulcers). Among the 350 patients, 5 reported 9 adverse events (1.4%) and 335 preferred MCE over gastroscopy (95.7%). CONCLUSIONS: MCE detects focal lesions in the upper and lower stomach with comparable accuracy with conventional gastroscopy. MCE is preferred by almost all patients, compared with gastroscopy, and can be used to screen gastric diseases without sedation. Clinicaltrials.gov number: NCT02219529.

Factors predicting the technical difficulty of peroral endoscopic myotomy for achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) has been described as a novel treatment for esophageal achalasia. Owing to its technical difficulty, POEM is not widely performed. This study was aimed to prospectively assess the factor predicting technical difficulty of POEM in a single center with large volume cases. METHODS: A total of 105 cases of achalasia treated by POEM from April 2011 to September 2014 were analyzed. Difficult cases of POEM were defined as procedure time ≥90 min and occurrence of adverse events, including mucosal perforation, pneumothorax, and major bleeding. Univariate and multivariate logistic regression analyses were performed to assess the predictive factors of difficult POEM. RESULTS: POEM was successfully completed in all the patients, and no one was converted to laparoscopy. The number of cases with procedure time ≥90 min was 17. Mucosal perforations occurred in six (5.7 %) patients during submucosal tunnel creation, major bleeding occurred in seven (6.7 %) patients, and pneumothorax occurred in six (5.7 %) patients immediately after procedure. All the complications were managed conservatively. No other intraoperative and immediate postoperative complications, including infections and pneumoperitoneum, occurred. Multivariate analysis showed that early period (odds ratio [OR] 4.173, 95 % confidence interval [95 % CI] 1.36-6.829, P = 0.023) and triangular tip knife ([OR] 6.712, [95 % CI] 1.479-30.460, P = 0.014) were independent factors associated with technical difficulty regarding longer procedure time (procedure time ≥90 min). CONCLUSION: POEM is safe for the treatment of esophageal achalasia. Triangular tip knife and early period were independent risk factors for longer procedural time.

Comparison of conventional versus Hybrid knife peroral endoscopic myotomy methods for esophageal achalasia: a case-control study.

OBJECTIVE: Peroral endoscopic myotomy (POEM) has been developed to treat achalasia as a novel less invasive modality. We aimed to compare the efficacy and safety of conventional knife versus Hybrid knife (HK) during POEM procedure. MATERIALS AND METHODS: Between June 2012 and July 2014, 31 patients underwent POEM using HK in our department (HK group), and 36 patients underwent POEM using conventional method (injection needle and triangular tip [TT] knife, TT group). Procedure-related parameters, symptom relief, adverse events were compared between two groups. RESULTS: There were no significant differences in the age, sex and other baseline characteristics between the two groups. The mean procedural time was significantly shorter in HK group than TT group (53.0 ± 17.2 vs. 67.6 ± 28.4 min, p = 0.015). The mean frequency of devices exchange was 4.7 ± 1.7 in HK group and 10.9 ± 1.8 in TT group (p = 0.000). No serious adverse events occurred postoperatively in both groups. At one-year follow-up, a total of 94% treatment success was achieved in all patients (93.5% in HK group and 94.4% in TT group, p = 0.877). CONCLUSION: HK in POEM can shorten the procedural time, and achieve similar treatment success compared to conventional TT knife.

Lgr5 Methylation in Cancer Stem Cell Differentiation and Prognosis-Prediction in Colorectal Cancer.

OBJECTIVE: Leucine-rich-repeat-containing G-protein-coupled receptor 5 (lgr5) is a candidate marker for colorectal cancer stem cells (CSC). In the current study, we investigated the methylation status within thelgr5 promoter and evaluated its relationship with CSC differentiation, prognosis for colorectal cancer, and its clinicopathological features. METHODS: The methylation status within Lgr5 promoter was detected with a methylation-specific PCR in six colorectal cancer cell lines as well as 169 primary colorectal tumor tissues. Differentiation of CSC was examined with immunofluorescence and immunocytochemistry. Down-regulation of lgr5 was achieved with gene-specific siRNA. The associations between lgr5 methylation and the clinicopathological features as well as survival of patients were analyzed with statistical methods. RESULTS: The lgr5 promoter was methylated to different degrees for the six colorectal cell lines examined, with complete methylation observed in HCT116 cells in which the lgr5 expression was partially recovered following DAC treatment. The stem-cell sphere formation from HCT116 cells was accompanied by increasing methylation within the lgr5 promoter and decreasing expression of lgr5. Knocking down lgr5 by siRNA also led to stem-cell spheres formation. Among primary colorectal tumors, 40% (67/169) were positive for lgr5 methylation, while none of the normal colon tissues were positive for lgr5 methylation. Furthermore, lgr5 methylation significantly associated with higher tumor grade, and negative distant metastasis (p < 0.05), as well as better prognosis (p = 0.001) in patients with colorectal cancer. CONCLUSIONS: Our data suggests that lgr5 methylation, through the regulation of lgr5 expression and colorectal CSC differentiation, may constitute a novel prognostic marker for colorectal cancer patients.

Usefulness of peroral endoscopic myotomy for treating achalasia in children: experience from a single center.

INTRODUCTION: Achalasia is a rare esophageal motility disorder in the pediatric population. Peroral endoscopic myotomy (POEM) has been demonstrated to be effective and safe for the treatment of achalasia as a novel endoscopic technique, but data involving its utility in pediatric patients are limited. We aimed to assess the safety and efficacy of POEM for pediatric patients with achalasia. MATERIALS AND METHODS: Between July 2012 and August 2014, five consecutive pediatric patients (2 female and 3 male, with a median age of 15 years) with achalasia underwent POEM in our center. Diagnosis was based on symptoms, manometry, radiology and endoscopy. Preoperative and postoperative symptoms scores, and manometry outcomes were recorded and analyzed. RESULTS: Procedure was performed successfully in all patients, and the median time required for the procedure was 50 min (range 40-90 min). There were no mortalities and no serious intraoperative and postoperative complications. The median length of myotomy was 8 cm (range 6-11 cm). During a median follow-up period of 18 months, treatment success (Eckardt score ≤3) was achieved in all patients. There was a significant improvement of symptoms relief, dysphagia score and lower esophageal sphincter pressure decrease after POEM. No patient developed gastroesophageal reflux disease. CONCLUSION: Our study suggests that POEM is a safe and effective technique for treating pediatric achalasia. Further studies with long-term follow-up in large-volume pediatric patients are warranted to clearly define the durability of the procedure.

BRD4 inhibitor inhibits colorectal cancer growth and metastasis.

Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal.

Effects of simvastatin on glucose metabolism in mouse MIN6 cells.

The aim of this study was to investigate the effects of simvastatin on insulin secretion in mouse MIN6 cells and the possible mechanism. MIN6 cells were, respectively, treated with 0 µ M, 2 µ M, 5 µ M, and 10 µ M simvastatin for 48 h. Radio immunoassay was performed to measure the effect of simvastatin on insulin secretion in MIN6 cells. Luciferase method was used to examine the content of ATP in MIN6 cells. Real-time PCR and western blotting were performed to measure the mRNA and protein levels of inward rectifier potassium channel 6.2 (Kir6.2), voltage-dependent calcium channel 1.2 (Cav1.2), and glucose transporter-2 (GLUT2), respectively. ATP-sensitive potassium current and L-type calcium current were recorded by whole-cell patch-clamp technique. The results showed that high concentrations of simvastatin (5 µ M and 10 µ M) significantly reduced the synthesis and secretion of insulin compared to control groups in MIN6 cells (P < 0.05). ATP content in simvastatin-treated cells was lower than in control cells (P < 0.05). Compared with control group, the mRNA and protein expression of Kir6.2 increased with treatment of simvastatin (P < 0.05), and mRNA and protein expression of Cav1.2 and GLUT2 decreased in response to simvastatin (P < 0.05). Moreover, simvastatin increased the ATP-sensitive potassium current and reduced the L-type calcium current. These results suggest that simvastatin inhibits the synthesis and secretion of insulin through a reduction in saccharometabolism in MIN6 cells.

Serum antibodies to microbial antigens for Crohn's disease progression: a meta-analysis.

OBJECTIVES: This meta-analysis evaluated the stratification powers of four well-studied serum antibodies to microbial antigens [ASCA (anti-Saccharomyces cerevisiae), anti-OmpC (anti-outer-membrane protein C), anti-I2 (anti-Pseudomonas fluorescens-associated sequence I2), and anti-CBir1 (anti-bacterial flagellin)] in characterizing progression of Crohn's disease (CD). METHODS: Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CI) for individual antibodies and antibody combination were used to evaluate and compare their stratification powers for CD-related complications and the need for surgery. RESULTS: Eleven studies were included in this meta-analysis. In terms of the outcomes for CD complication and surgery, ASCA had the highest sensitivities at 0.66 (CI 0.63-0.69) for complications and 0.66 (CI 0.63-0.68) for surgery, whereas anti-OmpC had the highest specificities at 0.83 (CI 0.80-0.85) for complications and 0.81 (CI 0.79-0.83) for surgery. Anti-OmpC had the highest DORs at 2.61 (CI 2.16-3.15) for complications and 2.93 (CI 2.48-3.47) for surgery, and a combination of at least two antibodies presented pooled DORs at 2.93 (CI 2.42-3.56) for complications and 3.39 (CI 2.73-4.20) for surgery, superior to any single antibody. CONCLUSION: Anti-OmpC had the highest stratification power among the four antibodies screened for the risk of both complications and surgery in CD patients, and the power became stronger when antibodies were assessed in combination.

Epigenetic silencing of miR-126 contributes to tumor invasion and angiogenesis in colorectal cancer.

microRNAs (miRNAs) have been reported to play a crucial role in regulating a variety of genes pivotal for tumor metastasis. miR-126 is well known as one of the angiogenesis regulatory miRNAs. Recent studies have reported controversial roles of miR-126 in tumor progression. In this study, we sought to investigate the potential roles of miR-126 in colorectal cancer (CRC). By real-time PCR, miR-126 was shown to be downregulated in primary CRC tissues and cell lines. Restoration of miR-126 in CRC cells inhibited cell growth, migration and invasion. Using both in silico prediction and immunoblotting, we found that vascular endothelial growth factor (VEGF) was a target of miR-126. The interaction of miR-126 on the 3'UTR of VEGF mRNA was validated by luciferase reporter assay. Mechanistically, we found that the silencing of miR-126 was induced by promoter methyl-ation of its host gene, EGFL7. Treatment with 5-aza-CdR restored miR-126 expression and thereby led to a decline in VEGF expression. Functionally, due to suppression of VEGF, enhanced miR-126 expression inhibited tumor neovasculature triggered by CRC cells. In conclusion, our findings suggest that DNA methylation-induced silencing of miR-126 contributes, at least in part, to tumor invasion and angiogenesis in CRC, through upregulation of VEGF expression. miR-126 may be a potential target for the therapeutic strategy against CRC.