4.7 Article

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

Journal

INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 11, Issue -, Pages 5871-5881

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S114838

Keywords

Hirschsprung's disease; neuronal development; exosomal long noncoding RNA; intercellular communication; apoptosis; mitochondria

Funding

  1. Natural Science Foundation of China (NSFC) [81370473, 81400574, 81570467]
  2. Natural Science Foundation of Jiangsu Province of China [BK20131388]
  3. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)

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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.

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