title: miRNA Profiling Reveals Dysregulation of RET and RET-Regulating Pathways in Hirschsprung's Disease.
abstract: Hirschsprung's disease (HSCR), the most common congenital malformation of the gut, is regulated by multiple signal transduction pathways. Several components of these pathways are important targets for microRNAs (miRNAs). Multiple miRNAs have been associated with the pathophysiology of HSCR, and serum miRNAs profiles of HSCR patients have been reported, but miRNA expression in HSCR colon tissue is almost completely unexplored. Using microarray technology, we screened colon tissue to detect miRNAs whose expression profiles were altered in HSCR and identify targets of differentially expressed miRNAs. Following filtering of low-intensity signals, data normalization, and volcano plot filtering, we identified 168 differentially expressed miRNAs (104 up-regulated and 64 down-regulated). Fifty of these mRNAs represent major targets of dysegulated miRNAs and may thus important roles in the pathophysiology of HSCR. Pathway analysis revealed that 7 of the miRNA targets encode proteins involved in regulation of cell proliferation and migration via RET and related signaling pathways (MAPK and PI3K/AKT). Our results identify miRNAs that play key roles in the pathophysiology of the complex multi-factorial disease HSCR.
authors.affiliation: Tumour laboratory of Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, PR China.|Department of Gastrointestinal Surgery and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Tumour laboratory of Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, PR China.|Department of Gastrointestinal Surgery and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Tumour laboratory of Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, PR China.|Department of Gastrointestinal Surgery and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Tumour laboratory of Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, PR China.|Department of Gastrointestinal Surgery and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Tumour laboratory of Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, PR China.|Department of Gastrointestinal Surgery and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Gastrointestinal Surgery and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery and Neonatal Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Li
authors.affiliation: Tumour laboratory of Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Key Laboratory of Pediatrics in Chongqing, Children's Hospital of Chongqing Medical University, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, PR China.
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Liang
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D002675:Child, Preschool; D003106:Colon / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006627:Hirschsprung Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D035683:MicroRNAs / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051096:Proto-Oncogene Proteins c-ret; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases