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

Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p.
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DOI:
10.3390/ijms222212453
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发表时间:
2021-11-18
影响因子:
5.6
通讯作者:
Iwata J
Iwata J
中科院分区:
生物学2区
文献类型:
--
作者:
Yoshioka H;Jun G;Suzuki A;Iwata J

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唇裂伴或不伴腭裂(CL/P)是最常见的先天性先天性缺陷之一。本研究旨在鉴定与腭裂(CP)相关的新型致病microrna。通过对发育中的C57BL/6J小鼠腭架的mirna测序数据分析,我们发现在胚胎期E14.5与E13.5相比,miR-449a-3p、miR-449a-5p、miR-449c-3p和miR-449c-5p显著上调,miR-19a-3p、miR-130a-3p、miR-301a-3p和miR-486b-5p显著下调。其中,miR-449家族(miR-449a-3p、miR-449a-5p、miR-449b、miR-449c-3p和miR-449c-5p)和miR-486b-5p的过表达导致原代小鼠胚胎腭间充质(MEPM)细胞和小鼠颅神经嵴细胞系O9-1细胞增殖减少。另一方面,miR-130a-3p和miR-301a-3p抑制剂显著降低MEPM和O9-1细胞的细胞增殖。值得注意的是,我们发现用地塞米松(一种已知在小鼠中诱导CP的糖皮质激素)治疗可以抑制MEPM和O9-1细胞中miR-130a-3p的表达。此外,miR-130a-3p模拟物可以通过正常化Slc24a2的表达来改善地塞米松诱导的细胞增殖缺陷。综上所述,我们的结果表明miR-130-3p在小鼠地塞米松诱导的CP中起着至关重要的作用。
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.
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