MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

Yoshioka, Hiroki; Mikami, Yurie; Ramakrishnan, Sai Shankar; Suzuki, Akiko; Iwata, Junichi

doi:10.3389/fcell.2021.621045

Cited by 17 publications

(15 citation statements)

References 87 publications

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“…MEPM cell migration and proliferation play significant roles in the formation of facial structures (He et al, 2008). Many studies have investigated whether atRA inhibits MEPM cell proliferation (Liu et al, 2016;Liu et al, 2021;Yoshioka et al, 2021;. However, the molecular mechanism by which HSL affects cell migration and proliferation needs to be fully clarified.…”

Section: Discussionmentioning

confidence: 99%

The involvement of hormone-sensitive lipase in all-trans retinoic acid induced cleft palate

Zheng¹,

Ye²

2022

Int. J. Dev. Biol.

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Abnormally high concentrations of all-trans retinoic acid (atRA) induce cleft palate, which is accompanied by abnormal migration and proliferation of mouse embryonic palatal mesenchyme (MEPM) cells. Hormone-sensitive lipase (HSL) is involved in many embryonic development processes. The current study was designed to elucidate the mechanism of HSL in cleft palate induced by atRA. To establish a cleft palate model in Kunming mice, pregnant mice were administered atRA (70 mg/kg) by gavage at embryonic Day 10.5 (E10.5). Embryonic palates were obtained through the dissection of pregnant mice at E15.5. Hematoxylin and eosin (H&E) staining was used to evaluate growth changes in the palatal shelves. The levels of HSL in MEPM cells were detected by immunohistochemistry, quantitative real-time reverse transcription-polymerase chain reaction (qRT‒PCR) and western blotting. RNAi was applied to construct vectors expressing HSL small interference RNAs (siRNAs). The vectors were transfected into MEPM cells. Cell proliferation and migration were evaluated by the cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. The palatal shelves in the atRA group had separated at E15.5 without fusing. In MEPM cells, the expression of HSL was reversed after atRA treatment, which caused cleft palate in vivo. In the atRA group, the proliferation of HSL siRNA-transfected cells was remarkably promoted, and the migration rate significantly increased in the HSL siRNA-transfected MEPM cells. These results suggested that HSL may be involved in cleft palate induced by atRA and that atRA enhances HSL levels to inhibit embryonic palate growth.

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Section: Discussionmentioning

confidence: 99%

The involvement of hormone-sensitive lipase in all-trans retinoic acid induced cleft palate

Zheng¹,

Ye²

2022

Int. J. Dev. Biol.

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“…Excessive atRA, DEX, and phenytoin induce CP in mice [24,39,40]. Excessive atRA induces CP through upregulated miR-124-3p expression [11], and DEX induces miR-130b and miR-155 in porcine pre-adipocytes and differentiating 3T3-L1 pre-adipocytes, respectively [41,42]. DEX also inhibits miR-132 expression through TGF-β signaling in pancreatic cancer [43].…”

Section: Discussionmentioning

confidence: 99%

“…We have previously reported that overexpression of miR-374a, miR-133b, and miR-4680-3p inhibits cell proliferation in cultured human palatal mesenchymal cells [9]. In addition, exposure to all-trans retinoic acid (atRA) alters the expression of miR-106-5p [10] and miR-124-3p [11] in mouse embryonic palatal shelves. A growing amount of evidence shows that miRNAs play crucial roles in development and pathological conditions; therefore, it is important to identify how the expression of miRNAs is altered under specific conditions and in presence of chemicals known to cause of CP.…”

Section: Introductionmentioning

confidence: 99%

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

Yoshioka

Jun

Suzuki

et al. 2021

IJMS

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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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“…Exposure to several chemicals (e.g., retinoic acid, dexamethasone, dioxins) induces cleft palate in mice and in humans [ 124 , 125 , 126 ]. Retinoic acid ( at RA) induces expression of miR-124-3p [ 127 , 128 ] and miR-106-5p [ 129 ] in cultured MEPM cells and the developing palatal shelves in mice. miR-124-3p can inhibit cell proliferation through suppression of genes crucial for palate development, and miR-106-5p induces apoptosis and compromises phosphatidylcholine synthesis/cell membrane synthesis though suppression of Tgfbr2 .…”

Section: Micrornas Involved In Chemical-induced Cleft Lip and Cleft P...mentioning

confidence: 99%

MicroRNAs and Gene Regulatory Networks Related to Cleft Lip and Palate

Iwaya

Suzuki

Iwata

2023

IJMS

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Cleft lip and palate is one of the most common congenital birth defects and has a complex etiology. Either genetic or environmental factors, or both, are involved at various degrees, and the type and severity of clefts vary. One of the longstanding questions is how environmental factors lead to craniofacial developmental anomalies. Recent studies highlight non-coding RNAs as potential epigenetic regulators in cleft lip and palate. In this review, we will discuss microRNAs, a type of small non-coding RNAs that can simultaneously regulate expression of many downstream target genes, as a causative mechanism of cleft lip and palate in humans and mice.

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MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

Cited by 17 publications

References 87 publications

The involvement of hormone-sensitive lipase in all-trans retinoic acid induced cleft palate

The involvement of hormone-sensitive lipase in all-trans retinoic acid induced cleft palate

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

MicroRNAs and Gene Regulatory Networks Related to Cleft Lip and Palate

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