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

miR-155-5p 通过靶向 FOXO3 和 CDKN1B 促进外阴硬化性苔藓中的成纤维细胞增殖并抑制 FOXO 信号通路

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作者:Lina Ren, Yi Zhao, Xiaoxi Huo, Xin Wu

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.

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