mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate.
Epigenetics
; 17(13): 2278-2295, 2022 12.
Article
en En
| MEDLINE
| ID: mdl-36047706
ABSTRACT
Non-syndromic cleft lip with or without cleft palate (NSCLP), the most common human craniofacial malformation, is a complex disorder given its genetic heterogeneity and multifactorial component revealed by genetic, epidemiological, and epigenetic findings. Epigenetic variations associated with NSCLP have been identified; however, functional investigation has been limited. Here, we combined a reanalysis of NSCLP methylome data with genetic analysis and used both in vitro and in vivo approaches to dissect the functional effects of epigenetic changes. We found a region in mir152 that is frequently hypomethylated in NSCLP cohorts (21-26%), leading to mir152 overexpression. mir152 overexpression in human neural crest cells led to downregulation of spliceosomal, ribosomal, and adherens junction genes. In vivo analysis using zebrafish embryos revealed that mir152 upregulation leads to craniofacial cartilage impairment. Also, we suggest that zebrafish embryonic hypoxia leads to mir152 upregulation combined with mir152 hypomethylation and also analogous palatal alterations. We therefore propose that mir152 hypomethylation, potentially induced by hypoxia in early development, is a novel and frequent predisposing factor to NSCLP.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Labio Leporino
/
Fisura del Paladar
/
MicroARNs
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Epigenetics
Asunto de la revista:
GENETICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Brasil