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

Abstract 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, incl...

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Main Authors: E. Yang, Luqi Xue, Zhengyu Li, Tao Yi
Format: Article
Language:English
Published: BMC 2019-07-01
Series:BMC Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12885-019-5775-1
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spelling doaj-e72cd63c469e4071b2a944d314cf465a2020-11-25T02:56:32ZengBMCBMC Cancer1471-24072019-07-0119111110.1186/s12885-019-5775-1Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5pE. Yang0Luqi Xue1Zhengyu Li2Tao Yi3Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan UniversityDepartment of Gynecology and Obstetrics, West China Second University Hospital, Sichuan UniversityDepartment of Gynecology and Obstetrics, West China Second University Hospital, Sichuan UniversityKey Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan UniversityAbstract 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.http://link.springer.com/article/10.1186/s12885-019-5775-1Multiple uterine leiomyomaSolitary uterine leiomyomaLong non-coding RNAsmicroRNAs
collection DOAJ
language English
format Article
sources DOAJ
author E. Yang
Luqi Xue
Zhengyu Li
Tao Yi
spellingShingle E. Yang
Luqi Xue
Zhengyu Li
Tao Yi
Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p
BMC Cancer
Multiple uterine leiomyoma
Solitary uterine leiomyoma
Long non-coding RNAs
microRNAs
author_facet E. Yang
Luqi Xue
Zhengyu Li
Tao Yi
author_sort E. Yang
title Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p
title_short Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p
title_full Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p
title_fullStr Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p
title_full_unstemmed Lnc-AL445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with miR-146b-5p
title_sort lnc-al445665.1–4 may be involved in the development of multiple uterine leiomyoma through interacting with mir-146b-5p
publisher BMC
series BMC Cancer
issn 1471-2407
publishDate 2019-07-01
description Abstract 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.
topic Multiple uterine leiomyoma
Solitary uterine leiomyoma
Long non-coding RNAs
microRNAs
url http://link.springer.com/article/10.1186/s12885-019-5775-1
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