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微小RNA-155-5p通过靶向FOXO3和细胞周期蛋白依赖性激酶抑制剂1B促进外阴硬化性苔藓中真皮成纤维细胞增殖并抑制FOXO信号通路。

MiR-155-5p promotes fibroblast cell proliferation and inhibits FOXO signaling pathway in vulvar lichen sclerosis by targeting FOXO3 and CDKN1B.

作者信息

Ren Lina, Zhao Yi, Huo Xiaoxi, Wu Xin

机构信息

Department of Gynecology and Obstetrics, The First Affiliated Hospital of China Medical University, Liaoning 110001, China.

Department of Obstetrics and Gynecology, Army General Hospital, Beijing 100700, China.

出版信息

Gene. 2018 May 5;653:43-50. doi: 10.1016/j.gene.2018.01.049. Epub 2018 Jan 12.

Abstract

Vulvar lichen sclerosis (VLS) is a chronic inflammatory skin disorder. Evidence is accumulating that microRNAs (miRNAs) exert crucial roles in initiation and development of a wide range of human diseases. MiR-155-5p has been frequently reported to be implicated in the tumorigenesis and progression of multiple types of cancers, however, its biological role in VLS remains unclear. This study aimed to explore the role of miR-155-5p in VLS and clarify the potential molecular mechanisms involved. In the present study, miR-155-5p was observed to be significantly upregulated in VLS tissues. Functional studies showed that miR-155-5p facilitated cell proliferation, accelerated cell cycle progression and inhibited forkhead box O (FOXO) signaling pathway in fibroblast cells. Mechanical studies demonstrated that miR-155-5p exerted its promoting effects on fibroblast cell proliferation via targeting both forkhead box O3 (FOXO3) and cyclin-dependent kinase inhibitor 1B (CDKN1B). Besides, Pearson's correlation analysis revealed that miR-155-5p expression was negatively correlated with the mRNA expression of FOXO3 and CDKN1B in VLS tissues. Taken together, our results indicate that miR-155-5p promotes fibroblast cell proliferation and inhibits FOXO signaling pathway by negative modulation of both FOXO3 and CDKN1B in VLS, and that miR-155-5p may be used to be a potential therapeutic target for VLS.

摘要

外阴硬化性苔藓(VLS)是一种慢性炎症性皮肤病。越来越多的证据表明,微小RNA(miRNA)在多种人类疾病的发生和发展中发挥着关键作用。MiR-155-5p经常被报道与多种类型癌症的肿瘤发生和进展有关,然而,其在VLS中的生物学作用仍不清楚。本研究旨在探讨miR-155-5p在VLS中的作用,并阐明其潜在的分子机制。在本研究中,观察到miR-155-5p在VLS组织中显著上调。功能研究表明,miR-155-5p促进成纤维细胞增殖,加速细胞周期进程,并抑制成纤维细胞中的叉头框O(FOXO)信号通路。机制研究表明,miR-155-5p通过靶向叉头框O3(FOXO3)和细胞周期蛋白依赖性激酶抑制剂1B(CDKN1B)对成纤维细胞增殖发挥促进作用。此外,Pearson相关性分析显示,VLS组织中miR-155-5p表达与FOXO3和CDKN1B的mRNA表达呈负相关。综上所述,我们的结果表明,miR-155-5p通过对VLS中FOXO3和CDKN1B的负调控促进成纤维细胞增殖并抑制FOXO信号通路,并且miR-155-5p可能成为VLS的潜在治疗靶点。

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