Research paperMiR-155-5p promotes fibroblast cell proliferation and inhibits FOXO signaling pathway in vulvar lichen sclerosis by targeting FOXO3 and CDKN1B
Introduction
Vulvar lichen sclerosis (VLS) is a chronic inflammatory skin disorder characterized by atrophy of the labia majora, clitoral adhesion and introital stenosis (Belotto et al., 2017; Carlson et al., 1998; Renaud-Vilmer et al., 2004). VLS, frequently complicated by the loss of normal vulvar architecture, occurs predominantly in the postmenopausal women (Lee et al., 2015; Oskay et al., 2007). Persisting pruritus and severe burning pain are frequent clinical symptoms of VLS (Boardman & Stockdale, 2008; Stewart, 2010). The use of superpotent topical corticosteroids (CTSs) is regarded as the first-line treatment to achieve remission of VLS. However, it is documented that prolonged use of CTSs could cause some complications, including burning sensation, erythema, swelling and blistering (Kazandi et al., 2010; Terras et al., 2014; Borghi et al., 2016). Thus, there is a pressing need to develop novel and effective therapeutic alternatives for VLS. Molecular target treatment may be a promising therapeutic strategy for VLS.
MicroRNAs (miRNAs) are a large type of endogenous, small (~22 nucleotides) and single-stranded non-coding RNA molecules, which exerts the role of gene expression regulation by sequence-specific binding to 3' untranslated regions (3'UTRs) of theirs target messenger RNA (mRNAs) (Rieger et al., 2013; Subramanian et al., 2014). Increasing evidence has revealed that abnormal expression of miRNAs is implicated in a wide range of human neoplasms and other pathological processes (De Melo et al., 2015; De Melo et al., 2016; Alsharafi et al., 2015). Thus, a better understanding of the biological functions of miRNAs may be helpful for developing effective therapies for human diseases.
MiR-155-5p has been reported to be up-regulated and act as an oncogene in numerous human cancers, including non-small lung cancer (Yang et al., 2013), gastric cancer (Zhu et al., 2016), osteosarcoma (Bhattacharya et al., 2016), colon cancer (Alhaidari et al., 2017), and colorectal cancer (Qu et al., 2015). Additionally, miR-155 has been found to serve as a key player in regulating dendritic cell development and apoptosis (Lu et al., 2011). However, the role of miR-155p in VLS remains unknown. This study aimed to explore the functional role of miR-155-5p in VLS and clarify the potential molecular mechanisms involved. In the present study, miR-155-5p was discovered to be remarkably up-regulated in VLS tissues. Functional studies revealed that miR-155-5p facilitated HFF-1 cell proliferation and cell cycle progression. Mechanical studies demonstrated that miR-155-5p promoted cell proliferation and cell cycle progression in VLS by targeting both FOXO3 and CDKN1B.
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Patients and tissue samples
Vulvar lichen sclerosis tissues and matched normal vulvar tissues were collected from 20 patients who underwent surgical therapy from Dec 2010 to March 2015 in First Affiliated Hospital of China Medical University (Shenyang, China). All clinical samples were immediately frozen in liquid nitrogen and then stored at −80 °C for further analysis. This study was approved by the Ethnics and Academic Committee of China Medical University. All patients enrolled in this study provided written informed
miR-155-5p is significantly upregulated in VLS tissues
Although miR-155-5p has frequently been reported to be involved in multiple types of human cancers, its role in VLS remains unclear. Initially, we detected the expression of miR-155-5p in 20 pairs of VLS tissues and corresponding normal vulvar tissues by qRT-PCR. As evident from qRT-PCR analysis, VLS tissues exhibited higher expression levels of miR-155-5p than matched normal vulvar tissues (Fig. 1). Our finding indicates that miR-155-5p may be involved in the pathogenesis and development of
Discussion
VLS, a chronic inflammatory skin disorder, has drawn increasing attention around the world. Evidence is accumulating that ectopic expression of miRNAs is implicated in the occurrence and development of a wide range of human malignancies and other diseases (De Melo et al., 2015; De Melo et al., 2016; Alsharafi et al., 2015). Thus, a better understanding of the biological functions of miRNAs may be helpful for developing novel therapeutic strategies for human disorders. Previous studies have
Acknowledgements
This study was funded by Liaoning Scientific Technology Plan Program (no. 2014021057).
Disclosure of conflict of interest
None.
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