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MiRNA-149 as a Candidate for Facial Clefting and Neural Crest Cell Migration.

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MicroRNAs, specifically miR-149, play a role in nonsyndromic cleft lip with or without palate (nsCL/P) development. This microRNA influences human neural crest cell migration, a key factor in facial formation.

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Nonsyndromic cleft lip with or without palate (nsCL/P) is a common birth defect with complex causes.
  • Human neural crest cells (hNCC) are crucial for facial development and implicated in nsCL/P.
  • Noncoding regulatory mechanisms, including microRNAs (miRNAs), are increasingly recognized in nsCL/P etiology.

Purpose of the Study:

  • To investigate the role of hNCC-expressed miRNAs in nsCL/P development.
  • To identify specific miRNAs and their targets involved in nsCL/P pathogenesis.
  • To elucidate the cellular and molecular mechanisms by which miRNAs contribute to nsCL/P.

Main Methods:

  • Systematic miRNA expression analysis in human-induced pluripotent stem cell-derived hNCC using microarrays.
  • Cross-referencing candidate miRNA loci with nsCL/P genome-wide association study data.
  • In vitro functional studies involving miR-149 overexpression/inhibition in hNCC and 3'RNA-Seq analysis.

Main Results:

  • 152 candidate miRNAs were identified, with miR-149 implicated in nsCL/P etiology.
  • Overexpression of miR-149 in hNCC led to differential expression of 604 genes, including known targets (TLR4, JUNB) and nsCL/P candidate genes (NOG, BMP4, PAX6).
  • miR-149 affected hNCC migration patterns and enriched pathways related to cartilage development and NCC differentiation.

Conclusions:

  • miR-149 is implicated in the etiology of nsCL/P.
  • The study suggests miR-149 influences nsCL/P through its regulation of hNCC migration.
  • These findings highlight the role of miRNAs in the multifactorial etiology of nsCL/P.