Dataset Information

MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.

ABSTRACT: BACKGROUND:MicroRNAs (MiR) may promote fibroid development via altered expression of genes involved in cell proliferation and ECM formation, and evidence supports aberrant expression of MicroRNA (MiR) 21a-5p in fibroids. The purpose of this study was to investigate the functional significance of MiR 21a-5p overexpression in the pathobiology of leiomyomata (fibroids). METHODS:A basic science experimental design using immortalized fibroid and myometrial cell lines derived from patient-matched specimens was used. Stable overexpression of MiR-21a-5p in an immortalized fibroid and patient matched myometrial cell line was achieved through lentiviral vector infection. Main outcome measures were MiR-21-5p overexpression, target gene and protein expression, collagen (COL1A1) production, cell proliferation, cell migration, and cell cycle stages of fibroid and myometrial immortalized cell lines. RESULTS:MiR-21a-5p was overexpressed to similar levels in fibroid and myometrial cell lines after lentiviral infection. Increased expression of miR-21 resulted in increased gene and protein expression of TGF-?3 in both fibroid and myometrial cells. Changes in expression of the ECM genes Fibronectin, Collagen 1A1, CTGF, Versican and DPT were seen in both fibroid and myometrial cells. Changes were also seen in Matrix Metalloproteinase (MMP) related genes including MMP 2, MMP 9, MMP 11 and Serpine 1 in both fibroid and myometrial cells. MiR-21 upregulation resulted in increased proliferation and migration in fibroid cells compared to myometrial cells. CONCLUSIONS:MiR-21a-5p overexpression results in changes in the expression of ECM mediators in both fibroid and myometrial cells, and increased cell proliferation in fibroid cells. These finding suggest a potential functional role of MiR-21a-5p in the development of uterine fibroids and warrant further investigation.

SUBMITTER: Cardozo ER

PROVIDER: S-EPMC5946472 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.

Cardozo Eden R ER Foster Rosemary R Karmon Anatte E AE Lee Amy E AE Gatune Leah W LW Rueda Bo R BR Styer Aaron K AK

Reproductive biology and endocrinology : RB&E 20180511 1

<h4>Background</h4>MicroRNAs (MiR) may promote fibroid development via altered expression of genes involved in cell proliferation and ECM formation, and evidence supports aberrant expression of MicroRNA (MiR) 21a-5p in fibroids. The purpose of this study was to investigate the functional significance of MiR 21a-5p overexpression in the pathobiology of leiomyomata (fibroids).<h4>Methods</h4>A basic science experimental design using immortalized fibroid and myometrial cell lines derived from patie ...[more]

PMID: 29747655

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Project description:BACKGROUND:The clinical behaviors and cytogenetics of solitary uterine leiomyomas (SUL) and multiple uterine leiomyomas (MUL) vary, which greatly affects the choice of treatments for reproductive-aged patients with leiomyomas. Our previous study demonstrated that a series of microRNAs, including miR-146b-5p, are dysregulated and play important roles in the development of SUL and MUL. Long non-coding RNAs (lncRNAs) can participate in the pathogenesis of several diseases by regulating the expression of microRNAs; however, their roles in regulating miR-146b-5b and in the pathology of leiomyomas are unclear. METHODS:Pair-matched uterine leiomyoma and adjacent normal myometrium tissue samples were collected from 37 patients with leiomyomas, including 15 with SUL and 22 with MUL. Six paired samples (three SUL and three MUL samples) were used for lncRNAs microarray analysis. Targeted lncRNAs were selected by bioinformatics analysis, and were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and a dual-luciferase reporter assay. Growth curve analysis and qRT-PCR were used to evaluate the effect of silencing the lncRNA lnc-AL445665.1-4 on cell proliferation and miR-146b-5p expression, respectively. RESULTS:There were 245 up-regulated and 243 down-regulated lncRNAs in SUL, and 119 up-regulated and 447 down-regulated lncRNAs in MUL. Fifty-five of the selected lncRNAs were predicted to target miR-146b-5p, which is up-regulated in SUL and down-regulated in MUL. Four lncRNAs were selected after Venn diagram analysis showing common dysregulation in the three groups. Lnc-AL445665.1-4 was selected for further exploration. qRT-PCR showed that lnc-AL445665.1-4 expression was significantly up-regulated in MUL compared with SUL in an additional 12 and 19 paired SUL-normal and MUL-normal samples, respectively. The dual-luciferase reporter assay demonstrated the presence of binding sites on lnc-AL445665.1 for miR-146b-5p. Silencing lnc-AL445665.1-4 not only inhibited cell proliferation but also negatively regulated the expression of miR-146b-5p. CONCLUSIONS:Our results suggest that lnc-AL445665.1-4 may be involved in the development of MUL by interacting with miR-146b-5p. Further investigation of the roles of lncRNAs and miRNAs may help to optimize the clinical management of leiomyoma patients. Lnc-AL445665.1-4 could be a novel target for genetic therapy or serve as a biomarker for predicting the recurrence of MUL in patients that have undergone myomectomy.

Dataset Information

MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.

Publications

MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.

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