MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid
Cleft lip with/without cleft palate (CL/P) is one of the most common congenital birth defects, showing the complexity of both genetic and environmental contributions [e.g., maternal exposure to alcohol, cigarette, and retinoic acid (RA)] in humans. Recent studies suggest that epigenetic factors, inc...
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Published in | Frontiers in cell and developmental biology Vol. 9; p. 621045 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
09.06.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Cleft lip with/without cleft palate (CL/P) is one of the most common congenital birth defects, showing the complexity of both genetic and environmental contributions [e.g., maternal exposure to alcohol, cigarette, and retinoic acid (RA)] in humans. Recent studies suggest that epigenetic factors, including microRNAs (miRs), are altered by various environmental factors. In this study, to investigate whether and how miRs are involved in cleft palate (CP) induced by excessive intake of
RA (
RA), we evaluated top 10 candidate miRs, which were selected through our bioinformatic analyses, in mouse embryonic palatal mesenchymal (MEPM) cells as well as in mouse embryos treated with
RA. Among them, overexpression of miR-27a-3p, miR-27b-3p, and miR-124-3p resulted in the significant reduction of cell proliferation in MEPM cells through the downregulation of CP-associated genes. Notably, we found that excessive
RA upregulated the expression of miR-124-3p, but not of miR-27a-3p and miR-27b-3p, in both
and
. Importantly, treatment with a specific inhibitor for miR-124-3p restored decreased cell proliferation through the normalization of target gene expression in
RA-treated MEPM cells and
RA-exposed mouse embryos, resulting in the rescue of CP in mice. Taken together, our results indicate that
RA causes CP through the induction of miR-124-3p in mice. |
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Bibliography: | Edited by: Sebastian Dworkin, La Trobe University, Australia This article was submitted to Molecular Medicine, a section of the journal Frontiers in Cell and Developmental Biology Reviewed by: Rahul N. Kanadia, University of Connecticut, United States; Jing Xiao, Dalian Medical University, China; Jo Huiqing Zhou, Radboud University Nijmegen, Netherlands; Johannes W. Von den Hoff, Radboud University Nijmegen Medical Centre, Netherlands |
ISSN: | 2296-634X 2296-634X |
DOI: | 10.3389/fcell.2021.621045 |