Faculty, Staff and Student Publications
Language
English
Publication Date
7-11-2025
Journal
Cells
DOI
10.3390/cells14141068
PMID
40710321
PMCID
PMC12293701
PubMedCentral® Posted Date
7-11-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Any failure in frontonasal development can lead to malformations at the middle facial region, such as frontonasal dysplasia, midfacial clefts, and hyper/hypotelorism. Various environmental factors influence morphogenesis through epigenetic regulations, including the action of noncoding microRNAs (miRNAs). However, it remains unclear how miRNAs are involved in the frontonasal development. In our analysis of publicly available miRNA-seq and RNA-seq datasets, we found that miR-28a-5p, miR-302a-3p, miR-302b-3p, and miR-302d-3p were differentially expressed in the frontonasal process during embryonic days 10.5 to 13.5 (E10.5–E13.5) in mice. Overexpression of these miRNAs led to a suppression of cell proliferation in cultured mouse embryonic frontonasal mesenchymal (MEFM) cells as well as in O9-1 cells, a cranial neural crest cell line. Through advanced bioinformatic analyses and miRNA-gene regulation assays, we identified that miR-28a-5p regulated a total of 25 genes, miR-302a-3p regulated 23 genes, miR-302b-3p regulated 22 genes, and miR-302d-3p regulated 20 genes. Notably, the expression of miR-302a/b/d-3p—unlike miR-28a-5p—was significantly upregulated by excessive exposure to all-trans retinoic acid (atRA) that induces craniofacial malformations. Inhibition of these miRNAs restored the reduced cell proliferation caused by atRA by normalizing the expression of target genes associated with frontonasal anomalies. Therefore, our findings suggest that miR-302a/b/d-3p plays a crucial role in the development of frontonasal malformations.
Keywords
MicroRNAs, Animals, Tretinoin, Mice, Gene Expression Regulation, Developmental, Cell Proliferation, Cell Line, craniofacial development, microRNA, retinoic acid
Published Open-Access
yes
Recommended Citation
, "miR-302a/b/d-3p Differentially Expressed During Frontonasal Development Is Sensitive to Retinoic Acid Exposure" (2025). Faculty, Staff and Student Publications. 1253.
https://digitalcommons.library.tmc.edu/uthsph_docs/1253