MicroRNA-4516-mediated regulation of MAPK10 relies on 3’UTR cis-acting variants and contributes to the altered risk of Hirschsprung disease

Hirschsprung disease (HSCR) is a life-threatening genetic disorder in which the enteric nervous system (ENS) is completely missing from the distal gut. However, the contribution of genetic factors to HSCR remains unclear. In this paper, we identify MAPK10 as a HSCR susceptibility gene, which is directly regulated by miR-4516, and interestingly, the regulatory mechanism is strongly affected by the cis-acting elements of MAPK10. We also find that miR-4516 regulates human neural cell migration in a MAPK10-dependent way. Our findings show a key role of miR-4516 and its direct target MAPK10 in HSCR risk, and highlight the general importance of cis– and posttranscriptional modulation for HSCR pathogenesis. (By Dr. Yang Wang, https://jmg.bmj.com/content/early/2020/02/17/jmedgenet-2019-106615 )

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