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Lnc-AL445665.1-4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p

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Abstract Background The clinical behaviors and cytogenetics of solitary uterine leiomyomas (SUL) and multiple uterine leiomyomas (MUL) vary. Our previous study demonstrated that miR-146b-5p played important roles in the development… Click to show full abstract

Abstract Background The clinical behaviors and cytogenetics of solitary uterine leiomyomas (SUL) and multiple uterine leiomyomas (MUL) vary. Our previous study demonstrated that miR-146b-5p played important roles in the development of SUL and MUL. Long non-coding RNAs (lncRNAs) can participate in the pathogenesis of several diseases by regulating 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 were used for lncRNAs microarray analysis. Targeted lncRNAs were selected by bioinformatics analysis, and were verified by 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 Fifty-five of the selected lncRNAs were predicted to target miR-146b-5p. 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 assaydemonstrated 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. 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. Legal entity responsible for the study Zhengyu Li and E. Yang. Funding Has not received any funding. All authors have declared no conflicts of interest.

Keywords: multiple uterine; mir 146b; mul; lnc al445665; development

Journal Title: Annals of Oncology
Year Published: 2019

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