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miR-203 通过靶向 survivin 抑制角质形成细胞干性。

miR-203 represses keratinocyte stemness by targeting survivin.

机构信息

Ashland, Global Skin Research Centre, Sophia Antipolis, France.

出版信息

J Cosmet Dermatol. 2022 Nov;21(11):6100-6108. doi: 10.1111/jocd.15147. Epub 2022 Jun 22.

DOI:10.1111/jocd.15147
PMID:35673958
Abstract

OBJECTIVE

The epidermis possesses the capacity to replace dying cells and to heal wounds, thanks to resident stem cells, which have self-renewal properties. In skin physiology, miRNAs have been shown to be involved in many processes, including skin and hair morphogenesis. Recently, differentiation of epidermal stem cells was shown to be promoted by the miR-203. The miR-203 is upregulated during epidermal differentiation and is of interest because of significant targets.

METHODS

By utilizing a bioinformatic tool, we identified a target site for miR-203 in the survivin mRNA. Silencing miR-203 was managed with the use of antagomir; the silencing of survivin was performed with a siRNA. Survivin expression was determined by qPCR or immunofluorescence in cultured cells, and by immunohistochemistry in skin sections. Involucrin expression was used as marker of keratinocyte differentiation. A rice extract with previously demonstrated anti-aging properties was evaluated on miR-203 modulation.

RESULTS

In this study, we identified a miR-203/survivin axis, important for epidermal homeostasis. We report that differentiation of keratinocyte is dependent on the level of miR-203 expression and that inhibition of miR-203 can increase the expression of survivin, an epidermal marker of stemness.

CONCLUSION

In summary, our findings suggest that miR-203 target 3'UTR region of survivin mRNA and directly represses survivin expression in the epidermis. The rice extract was identified as modulator of miR-203 and pointed out as a promising microRNA-based strategy in treating skin changes occurring with aging.

摘要

目的

由于表皮干细胞具有自我更新的特性,因此表皮具有替换死亡细胞和愈合伤口的能力。在皮肤生理学中,已经表明 miRNA 参与了许多过程,包括皮肤和毛发的形态发生。最近,表皮干细胞的分化被证明是由 miR-203 促进的。miR-203 在表皮分化过程中上调,由于其显著的靶标而受到关注。

方法

我们利用生物信息学工具,在 survivin mRNA 中鉴定出 miR-203 的靶位。通过使用 antagomir 来沉默 miR-203,通过 siRNA 来沉默 survivin。在培养细胞中通过 qPCR 或免疫荧光法,以及在皮肤切片中通过免疫组织化学法来检测 survivin 的表达。角蛋白细胞分化的标志物是 involucrin 的表达。具有先前证明的抗衰老特性的米提取物被用于评估对 miR-203 调节的影响。

结果

在这项研究中,我们鉴定出了 miR-203/survivin 轴,这对表皮稳态很重要。我们报告说,角质形成细胞的分化依赖于 miR-203 表达水平,并且抑制 miR-203 可以增加 survivin 的表达,survivin 是表皮干性的标志物。

结论

总之,我们的研究结果表明,miR-203 靶向 survivin mRNA 的 3'UTR 区域,并直接抑制表皮中 survivin 的表达。米提取物被鉴定为 miR-203 的调节剂,并指出它是一种有前途的基于 microRNA 的策略,可用于治疗与衰老相关的皮肤变化。

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