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上调的长链非编码 RNA5322 通过作为 microRNA-19b-3p 的 ceRNA 来升高 MAPK1 从而增强毛囊干细胞的增殖。

Up-regulated lncRNA5322 elevates MAPK1 to enhance proliferation of hair follicle stem cells as a ceRNA of microRNA-19b-3p.

机构信息

a The First Affiliated Hospital of Zhengzhou University , Zhengzhou , P.R. China.

b School of Life Sciences , Zhengzhou University , Zhengzhou , P.R. China.

出版信息

Cell Cycle. 2019 Jul;18(14):1588-1600. doi: 10.1080/15384101.2019.1624111. Epub 2019 Jun 15.

Abstract

Hair follicle stem cells (HFSCs), located in the bulge region of the follicle, maintain hair follicle growth and cycling. Long non-coding RNAs (lncRNAs), non-protein coding transcripts, are widely known to play critical roles in differentiation and proliferation of stem cells. Therefore, the current study aimed to explore the regulatory roles of lncRNA5322 in HFSCs proliferation and the underlying regulatory mechanisms. Initially, the expression patterns of lncRNA5322 and microRNA-19b-3p (miR-19b-3p) in HFSCs were detected. Subsequently, gain-and loss-of-functions analyses were conducted to explore the roles of lncRNA5322, miR-19b-3p and mitogen-activated protein kinase 1 (MAPK1) in cell proliferation, colony formation and apoptosis of HFSCs, with the expression of cyclin-dependent kinase (CDK)1 and CDK2 examined. Also, the interaction relationships among lncRNA5322, miR-19b-3p and MAPK1 were explored. Furthermore, a mouse model was established to detect the roles of lncRNA5322, miR-19b-3p, and MAPK1 in wound contraction and epidermal regeneration. Over-expressed lncRNA5322 was found to promote proliferation, colony formation ability but inhibit apoptosis of HFSCs, in addition to up-regulation of the expression of CDK1 and CDK2. LncRNA5322 was found to act as a ceRNA of miR-19b-3p which directly targeted MAPK1. Furthermore, up-regulation of lncRNA5322 enhanced wound contraction and epidermal regeneration by increasing the expression of MAPK1 through functioning as a ceRNA of miR-19b-3p. In summary, the results in this study suggested that lncRNA5322 serves as a ceRNA of miR-19b-3p to elevate the expression of MAPK1, ultimately promoting HFSCs proliferation, wound contraction and epidermal regeneration of mouse model.

摘要

毛囊干细胞(HFSCs)位于毛囊的隆起区域,维持着毛囊的生长和周期。长链非编码 RNA(lncRNA)是一类不编码蛋白质的转录本,广泛参与干细胞的分化和增殖。因此,本研究旨在探讨 lncRNA5322 在 HFSCs 增殖中的调控作用及其潜在的调控机制。首先,检测了 lncRNA5322 和 microRNA-19b-3p(miR-19b-3p)在 HFSCs 中的表达模式。随后,进行了 gain-and loss-of-functions 分析,以探讨 lncRNA5322、miR-19b-3p 和丝裂原活化蛋白激酶 1(MAPK1)在 HFSCs 增殖、集落形成和凋亡中的作用,同时检测了细胞周期蛋白依赖性激酶(CDK)1 和 CDK2 的表达。还探讨了 lncRNA5322、miR-19b-3p 和 MAPK1 之间的相互作用关系。此外,建立了小鼠模型,以检测 lncRNA5322、miR-19b-3p 和 MAPK1 在伤口收缩和表皮再生中的作用。结果发现,过表达 lncRNA5322 可促进 HFSCs 的增殖、集落形成能力,并抑制其凋亡,同时上调 CDK1 和 CDK2 的表达。lncRNA5322 可作为 miR-19b-3p 的 ceRNA,直接靶向 MAPK1。此外,上调 lncRNA5322 通过作为 miR-19b-3p 的 ceRNA 增加 MAPK1 的表达,从而增强了伤口收缩和表皮再生。综上所述,本研究结果表明,lncRNA5322 通过作为 miR-19b-3p 的 ceRNA 上调 MAPK1 的表达,最终促进 HFSCs 的增殖,促进了小鼠模型的伤口收缩和表皮再生。

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