Department of Pharmacy, Gifu University of Medical Science, 4-3-3 Nijigaoka, Kani, Gifu, 509-0293, Japan.
Department Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8588, Japan.
Biochem Biophys Res Commun. 2024 Feb 12;696:149516. doi: 10.1016/j.bbrc.2024.149516. Epub 2024 Jan 14.
Cleft palate (CP) is one of the most common congenital diseases, and is accompanied by a complicated etiology. Medical exposure in women is among one of the reasons leading to CP. Recently, it has been reported that microRNA (miRNA) plays a crucial role in palate formation and the disruption of miRNA that influence the development of CP. Although association with pharmaceuticals and miRNAs were suggested, it has remained largely unknow. The aim of the current investigation is to elucidate upon the miRNA associated with the inhibition of phenobarbital (PB)-induced cell proliferation in human embryonic palatal mesenchymal (HEPM) cells. We showed that PB inhibited HEPM cell viability in a dose-dependent manner. We demonstrated that PB treatment suppressed cyclin-D1 expression in HEPM cells. Furthermore, PB upregulated let-7c-5p expression and downregulated the expression of two downstream genes (BACH1 and PAX3). Finally, we demonstrated that the let-7c-5p inhibitor alleviated PB-induced inhibition of cell proliferation and altered BACH1 and PAX3 expression levels. These results suggest that PB suppresses cell viability by modulating let-7c-5p expression.
腭裂 (CP) 是最常见的先天性疾病之一,其病因复杂。女性的医学暴露是导致 CP 的原因之一。最近有报道称,微小 RNA (miRNA) 在腭形成和干扰影响 CP 发育的 miRNA 中起着关键作用。尽管已经提出了与药物和 miRNA 的关联,但这在很大程度上仍然未知。目前的研究旨在阐明与抑制苯巴比妥 (PB) 诱导的人胚胎腭间充质 (HEPM) 细胞增殖相关的 miRNA。我们表明 PB 以剂量依赖的方式抑制 HEPM 细胞活力。我们证明 PB 处理抑制了 HEPM 细胞中环蛋白 D1 的表达。此外,PB 上调了 let-7c-5p 的表达,并下调了两个下游基因 (BACH1 和 PAX3) 的表达。最后,我们证明 let-7c-5p 抑制剂减轻了 PB 诱导的细胞增殖抑制作用,并改变了 BACH1 和 PAX3 的表达水平。这些结果表明,PB 通过调节 let-7c-5p 的表达来抑制细胞活力。