Abstract
Cleft lip with or without cleft palate (CL/P) is one of the most common congenital birth defects. This study aims to identify novel pathogenic microRNAs associated with cleft palate (CP). Through data analyses of miRNA-sequencing for developing palatal shelves of C57BL/6J mice, we found that miR-449a-3p, miR-449a-5p, miR-449b, miR-449c-3p, and miR-449c-5p were significantly upregulated, and that miR-19a-3p, miR-130a-3p, miR-301a-3p, and miR-486b-5p were significantly downregulated, at embryonic day E14.5 compared to E13.5. Among them, overexpression of the miR-449 family (miR-449a-3p, miR-449a-5p, miR-449b, miR-449c-3p, and miR-449c-5p) and miR-486b-5p resulted in reduced cell proliferation in primary mouse embryonic palatal mesenchymal (MEPM) cells and mouse cranial neural crest cell line O9-1. On the other hand, inhibitors of miR-130a-3p and miR-301a-3p significantly reduced cell proliferation in MEPM and O9-1 cells. Notably, we found that treatment with dexamethasone, a glucocorticoid known to induce CP in mice, suppressed miR-130a-3p expression in both MEPM and O9-1 cells. Moreover, a miR-130a-3p mimic could ameliorate the cell proliferation defect induced by dexamethasone through normalization of Slc24a2 expression. Taken together, our results suggest that miR-130-3p plays a crucial role in dexamethasone-induced CP in mice.
Highlights
Published: 18 November 2021Cleft lip with/without cleft palate (CL/P) is a relatively common congenital birth defect in humans that affects approximately 1 in 700 newborns worldwide [1]
Through secondary data analyses of the miRNA-seq and RNA-seq datasets available at FaceBase, we identified a total of nine miRNAs that were differentially expressed in the palate between E13.5 and E14.5, with a false discovery rate (FDR) < 0.05
2.2. miRNAs Involved in Cell Growth in mouse embryonic palatal mesenchymal (MEPM) and O9-1 Cells
Summary
Published: 18 November 2021Cleft lip with/without cleft palate (CL/P) is a relatively common congenital birth defect in humans that affects approximately 1 in 700 newborns worldwide [1]. The development of the secondary palate in mammals includes palatal shelf growth, elevation of the palatal shelves, fusion between paired palatal shelves, disappearance of the medial epithelial seam, and intramembranous ossification of the palatal processes of the premaxilla and palatine bone [2]. Secondary palate development initiates at embryonic day 11.5 (E11.5) with the formation of tissue folds overlying the future palatal shelves within the oral cavity. Cranial neural-crest-derived mesenchymal cells proliferate within the maxillary processes to form the palatal primordium, which further enlarges to develop the palatal shelves. The palatal shelves continuously grow vertically along the sides of the tongue by E13.5 and approximately at E14.0, they elevate to a horizontal position above the tongue. At E14.5, Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
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