title: Long none coding RNA HOTTIP/HOXA13 act as synergistic role by decreasing cell migration and proliferation in Hirschsprung disease.
abstract: Long noncoding RNAs (lncRNAs) have been confirmed to be associated with various human diseases. However, whether they are associated with Hirschsprung disease (HSCR) progression remains unclear. In this study, we designed the experiment to explore the relationship between lncRNA HOTTIP and HOXA13, and their pathogenicity to HSCR. Quantitative real-time PCR and Western blot were performed to detect the levels of lncRNA, mRNAs, and proteins in colon tissues from 79 patients with HSCR and 79 controls. Small RNA interference transfection was used to study the function experiments in human 293T and SK-N-BE cell lines. The cell viability and activities were detected by the transwell assays, CCK8 assay, and flow cytometry, respectively. LncRNA HOTTIP and HOXA13 were significantly down-regulated in HSCR compared to the controls. Meanwhile, the declined extent of their expression levels makes sense between two main phenotype of HSCR. SiRNA-mediated knock-down of HOTTIP or HOXA13 correlated with decreased levels of each other and both reduced the cell migration and proliferation without affecting cell apoptosis or cell cycle. Our study demonstrates that aberrant reduction of HOTTIP and HOXA13, which have a bidirectional regulatory loop, may play an important role in the pathogenesis of HSCR.
authors.affiliation: Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Institute of Toxicology, School of Public Health, Nanjing Medical University, Ministry of Education, Nanjing 211166, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Institute of Toxicology, School of Public Health, Nanjing Medical University, Ministry of Education, Nanjing 211166, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Institute of Toxicology, School of Public Health, Nanjing Medical University, Ministry of Education, Nanjing 211166, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Institute of Toxicology, School of Public Health, Nanjing Medical University, Ministry of Education, Nanjing 211166, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Institute of Toxicology, School of Public Health, Nanjing Medical University, Ministry of Education, Nanjing 211166, China.
authors.forename: Pingfa
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Institute of Toxicology, School of Public Health, Nanjing Medical University, Ministry of Education, Nanjing 211166, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Anhui Provincial Children's Hospital, Anhui 230000, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Institute of Toxicology, School of Public Health, Nanjing Medical University, Ministry of Education, Nanjing 211166, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Institute of Toxicology, School of Public Health, Nanjing Medical University, Ministry of Education, Nanjing 211166, China. Electronic address: twbcn@njmu.com.
authors.forename: Weibing
authors.initials: W
authors.lastname: Tang
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D006627:Hirschsprung Disease / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018398:Homeodomain Proteins; D062085:RNA, Long Noncoding; C099959:homeobox protein HOXA13
keywords: HSCR; Hox genes; Long noncoding RNA; Neural cell; Pediatric disease