Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p

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-449...

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Autores principales: Hiroki Yoshioka, Goo Jun, Akiko Suzuki, Junichi Iwata
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:1c1444a23dcb476fa251f20619bf19892021-11-25T17:56:49ZDexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p10.3390/ijms2222124531422-00671661-6596https://doaj.org/article/1c1444a23dcb476fa251f20619bf19892021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12453https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Cleft 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 <i>Slc24a2</i> expression. Taken together, our results suggest that miR-130-3p plays a crucial role in dexamethasone-induced CP in mice.Hiroki YoshiokaGoo JunAkiko SuzukiJunichi IwataMDPI AGarticleenvironmental factorcleft palatemicroRNAgene regulationcell proliferationbirth defectBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12453, p 12453 (2021)
institution DOAJ
collection DOAJ
language EN
topic environmental factor
cleft palate
microRNA
gene regulation
cell proliferation
birth defect
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle environmental factor
cleft palate
microRNA
gene regulation
cell proliferation
birth defect
Biology (General)
QH301-705.5
Chemistry
QD1-999
Hiroki Yoshioka
Goo Jun
Akiko Suzuki
Junichi Iwata
Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p
description 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 <i>Slc24a2</i> expression. Taken together, our results suggest that miR-130-3p plays a crucial role in dexamethasone-induced CP in mice.
format article
author Hiroki Yoshioka
Goo Jun
Akiko Suzuki
Junichi Iwata
author_facet Hiroki Yoshioka
Goo Jun
Akiko Suzuki
Junichi Iwata
author_sort Hiroki Yoshioka
title Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p
title_short Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p
title_full Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p
title_fullStr Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p
title_full_unstemmed Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p
title_sort dexamethasone suppresses palatal cell proliferation through mir-130a-3p
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/1c1444a23dcb476fa251f20619bf1989
work_keys_str_mv AT hirokiyoshioka dexamethasonesuppressespalatalcellproliferationthroughmir130a3p
AT goojun dexamethasonesuppressespalatalcellproliferationthroughmir130a3p
AT akikosuzuki dexamethasonesuppressespalatalcellproliferationthroughmir130a3p
AT junichiiwata dexamethasonesuppressespalatalcellproliferationthroughmir130a3p
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