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Tang W.,Nanjing Medical University | Li H.,Nanjing Medical University | Tang J.,Nanjing Medical University | Wu W.,Nanjing Medical University | And 11 more authors.
Journal of Cellular and Molecular Medicine | Year: 2014

Hirschsprung's disease (HSCR), a congenital gastrointestinal disorder, is one of the most common causes of neonatal bowel obstruction. Without an early screening and diagnosis, some patients develop serious complications, such as toxic megacolon or acute enterocolitis. We sought to identify specific serum microRNAs (miRNAs) that can serve as novel early, non-invasive screening signature and then to test their specificity and sensitivity in diagnosing Hirschsprung's disease. We obtained serum samples from 95 HSCR cases and 104 matched controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR arranged in the training and a two-stage validation set. Additional double-blind testing was performed in 23 patients with clinically suspected HSCR to evaluate the diagnostic value and accuracy of the serum miRNA profile in predicting HSCR. Following a multi-stage evaluation approach, five miRNAs were significantly increased in HSCR cases compared with controls. The areas under the receiver operating characteristic (ROC) curve of this five-serum miRNA signature were 0.895, 0.893 and 0.925 in training set and two validation sets, respectively. The accuracy rate of the five-miRNA profile as HSCR signature was 82.6%, which, in the double-blind testing set, was markedly higher than that of contrast enema (70%), the most commonly used test performed to diagnose HSCR. Our results indicate that a fiveserum miRNA signature may be linked to HSCR, representing a potential, novel, non-invasive diagnostic approach for early screening of HSCR. © 2014 The Authors.

Lei H.,Nanjing Medical University | Tang J.,Nanjing Medical University | Li H.,Nanjing Medical University | Zhang H.,Xuzhou Childrens Hospital Affiliated Xuzhou Medical University | And 5 more authors.
BMC Gastroenterology | Year: 2014

Background: Hirschsprung's disease (HSCR) is the most common congenital gut motility disorder. We aimed to investigate the roles of miR-195 in the pathogenesis of HSCR.Methods: In this study, we measured the expression levels of miRNA, mRNA, and protein in colon tissues from 78 patients with HSCR and 66 controls without HSCR. Transwell, Cell Counting Kit-8 (CCK-8) and flow cytometry assay were employed to detect the function role of miR-195 in vitro.Results: Our results showed that expression levels of miR-195 from patients with HSCR were significantly higher than control group; along with aberrant lower expression levels of digestive-organ expansion factor (DIEXF) were tested. Increased level of miR-195 could suppress the level of DIEXF in cell, which induced the impairment of cell migration and proliferation.Conclusions: Aberrant expression of miR-195 may involved in the pathogenesis of HSCR by down-regulated the level of DIEXF. © 2014 Lei et al.; licensee BioMed Central Ltd.

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