Apoptotic neuron-secreted HN12 inhibits cell apoptosis in Hirschsprung's disease

Abstract

Chunxia Du,1,2,* Hua Xie,1,2,* Rujin Zang,1,2,* Ziyang Shen,1,2 Hongxing Li,1,2 Pingfa Chen,1,2 Xiaoqun Xu,1,2 Yankai Xia,2,3 Weibing Tang1,2 1Department of Pediatric Surgery, Nanjing Children’s Hospital Affiliated to Nanjing Medical University, 2State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, 3Key Laboratory of Modern Toxicology, Ministry of Education, Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Perturbation in apoptosis can lead to Hirschsprung’s disease (HSCR), which is a genetic disorder of neural crest development. It is believed that long noncoding RNAs (lncRNAs) play a role in the progression of HSCR. This study shows that apoptotic neurons can suppress apoptosis of nonapoptotic cells by secreting exosomes that contain high levels of HN12 lncRNA. Elevated exogenous HN12 in nonapoptotic cells effectively inhibited cell apoptosis by maintaining the function of mitochondria, including the production of ATP and the release of cytochrome C. These results demonstrate that secreted lncRNAs may serve as signaling molecules mediating intercellular communication in HSCR. In addition, high HN12 levels in the circulation worked as a biomarker for predicting HSCR, providing a potential, novel, noninvasive diagnostic approach for early screening of HSCR. Keywords: Hirschsprung’s disease, neuronal development, exosomal long noncoding RNA, intercellular communication, apoptosis, mitochondria

Keywords

• Hirschsprung disease
• Neuronal development
• Exosomal long non-coding RNA
• Intercellular communication
• Apoptosis
• Mitochondria