title: Negative feedback circuitry between MIR143HG and RBM24 in Hirschsprung disease.
abstract: Hirschsprung disease (HSCR) is a genetic disorder of neural crest development. It is also believed that epigenetic changes plays a role in the progression of this disease. Here we show that the MIR143 host gene (MIR143HG), the precursor of miR-143 and miR-145, decreased cell proliferation and migration and forms a negative feedback loop with RBM24 in HSCR. As RBM24 mRNA is a target of miR-143, upregulation of RBM24 upon an increase in the level of MIR143HG could be attributed to sequestration of miR-143 by MIR143HG (sponge effect). The RBM24 protein was shown to bind to MIR143HG, and subsequently, accelerated its degradation by destabilizing its transcript and facilitating its interaction with Ago2, thus forming a negative feedback between MIR143HG and RBM24. In addition, experiments using siRNA against DROSHA indicated that RBM24 could promote the biogenesis of miR-143. This feedback loop we describe here represents a novel mode of autoregulation, with implications in HSCR pathogenesis.
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China.
authors: Chunxia
authors: C
authors: Du
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China.
authors: Ziyang
authors: Z
authors: Shen
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China.
authors: Rujin
authors: R
authors: Zang
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China.
authors: Hua
authors: H
authors: Xie
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China.
authors: Hongxing
authors: H
authors: Li
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China.
authors: Pingfa
authors: P
authors: Chen
authors: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors: Bo
authors: B
authors: Hang
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China.
authors: Xiaoqun
authors: X
authors: Xu
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China. Electronic address: twbcn@163.com.
authors: Weibing
authors: W
authors: Tang
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, China. Electronic address: yankaixia@njmu.edu.cn.
authors: Yankai
authors: Y
authors: Xia
keywords: Competing endogenous RNA (CeRNA); Hirschsprung disease; Long non-coding RNA (lncRNA); MiR-143; Neuronal development