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微小 RNA-31 通过靶向 Satb2 调节牙上皮细胞增殖。

MicroRNA-31 regulates dental epithelial cell proliferation by targeting Satb2.

机构信息

Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, PR China.

Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, PR China.

出版信息

Biochem Biophys Res Commun. 2020 Nov 5;532(2):321-328. doi: 10.1016/j.bbrc.2020.07.138. Epub 2020 Aug 30.

Abstract

MicroRNAs (miRNAs) exhibit strong potential clinical application owing to their extensive regulation and flexible delivery properties. MicroRNA-31 (miR-31) is an evolutionarily conserved miRNA expressed during tooth development, and it is highly expressed in mouse incisor epithelium. The specific role of miR-31 in odontogenesis has not been elucidated comprehensively, and the aim of the present study was to investigate its activity. Our results showed that miR-31 suppressed LS8 cell proliferation by inhibiting the cell cycle at the G1/S transition. Mutation of Special AT-rich sequence-binding protein 2 (SATB2) gene is responsible for human SATB2-associated syndrome (SAS), which is often accompanied by dental abnormities. Here, it was identified as a direct target of miR-31 in LS8 cells and a promoter of cell proliferation. The expression and distribution of SATB2 in mouse molars and incisors were explored using immunofluorescence, which showed strong signals in the nuclei of incisor epithelial cells and weak signals in the cytoplasm of molar epithelial cells. Moreover, rescue experiments demonstrated that Satb2 could mitigate the inhibitory effect of miR-31 on cell proliferation by promoting the expression of CDK4. Collectively, our results suggested that miR-31 regulates dental epithelial cell proliferation by targeting Satb2, highlighting the biological importance of miR-31 in odontogenesis.

摘要

微小 RNA(miRNAs)因其广泛的调节作用和灵活的递药特性而具有很强的临床应用潜力。miR-31 是一种在牙齿发育过程中表达的进化上保守的 miRNA,在小鼠切牙上皮中高度表达。miR-31 在牙齿发生中的具体作用尚未被全面阐明,本研究旨在探讨其活性。我们的结果表明,miR-31 通过抑制细胞周期在 G1/S 转换时抑制 LS8 细胞增殖。SATB2 基因的特殊 AT 富含序列结合蛋白 2(SATB2)基因突变是人类 SATB2 相关综合征(SAS)的原因,该综合征常伴有牙齿异常。在这里,它被鉴定为 LS8 细胞中 miR-31 的直接靶标,并促进细胞增殖。使用免疫荧光法探索了 SATB2 在小鼠磨牙和切牙中的表达和分布,结果显示在切牙上皮细胞的细胞核中存在强烈信号,而在磨牙上皮细胞的细胞质中存在较弱信号。此外,挽救实验表明 Satb2 可以通过促进 CDK4 的表达来减轻 miR-31 对细胞增殖的抑制作用。总之,我们的研究结果表明,miR-31 通过靶向 Satb2 调节牙上皮细胞增殖,突出了 miR-31 在牙齿发生中的重要生物学作用。

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