Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 26, 2019; 7(16): 2155-2164
Published online Aug 26, 2019. doi: 10.12998/wjcc.v7.i16.2155
Reduced microRNA-451 expression in eutopic endometrium contributes to the pathogenesis of endometriosis
Shan Gao, Shuang Liu, Zi-Ming Gao, Peng Deng, Dan-Bo Wang
Shan Gao, Shuang Liu, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
Zi-Ming Gao, Peng Deng, Department of Surgical Oncology and General Surgery, First Affiliated Hospital of China Medical University, Shenyang 110042, Liaoning Province, China
Dan-Bo Wang, Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
Author contributions: Gao S performed the majority of the experiments and analyzed the data; Liu S and Deng P performed the molecular investigations; Wang DB conceived and designed the experiments; Gao S and Gao ZM wrote the manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of China Medical University.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Dan-Bo Wang, MD, Professor, Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No. 44, Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China.
Telephone: +86-13840265165
Received: May 13, 2019
Peer-review started: May 21, 2019
First decision: July 30, 2019
Revised: August 6, 2019
Accepted: August 20, 2019
Article in press: August 20, 2019
Published online: August 26, 2019

Endometriosis (EMs) is a chronic and recurrent, but benign, disease in women of reproductive age, and EMs patients have a high risk of developing gynecological tumors and autoimmune disorders. The etiology of EMs is not clear. Certain genetic markers in the eutopic endometrium are key in the pathogenesis of EMs. MicroRNAs (miRNAs) are implicated in several biological processes, such as cell proliferation, differentiation, and apoptosis. MiR-451 is interesting, as it acts as a tumor suppressor and is relevant to the poor prognosis of cancers.


To evaluate the expression levels and role of miR-451 in the eutopic endometrium and predict possible targets of miR-451 and related signaling pathways.


Quantitative real-time polymerase chain reaction was used to evaluate miR-451 expression in cultured cell lines as well as in pathologic tissues from 40 patients with EMs and 20 donors with no history of the disease (controls). Cell Counting Kit-8 and flow cytometric assays were performed to determine cell proliferation and survival rates after transfection with miR-451 mimics and siRNAs. MiR-451 targets were predicted using miRDB and miRcode target-predicting databases.


We observed lower miR-451 levels in eutopic endometrial tissues from patients with EMs than in control tissues, and this difference was not related to the American Society for Reproductive Medicine stage. Ectopic overexpression of miR-451 in eutopic cells induced apoptosis and inhibited cell proliferation. SiRNA-mediated miR-451 knockdown reversed these effects. Using miRDB and miRcode, we identified 12 potential miR-451 target genes. We hypothesize that the expression of YWHAZ, OSR1, TTN, and CDKN2D may be regulated by miR-451 and be involved in disease pathogenesis.


Reduced miR-451 expression in the eutopic endometrium contributes to the pathogenesis of EMs by promoting cell proliferation and reducing apoptosis. Thus, miR-451 is a novel biomarker for EMs. YWHAZ, OSR1, TTN, and CDKN2D are potential target genes of miR-451 and may have key roles in this disease.

Keywords: Endometriosis, miR-451, Proliferation, Apoptosis, Pathogenesis

Core tip: Despite the high prevalence of endometriosis (EMs), its etiology is unclear. This study focuses on the expression of miR-451 in patients diagnosed with EMs. We report miR-451 as a novel biomarker of EMs as it is downregulated in the eutopic endometrium. YWHAZ, OSR1, TTN, and CDKN2D were identified as potential target genes of miR-451 that may have important roles in disease pathogenesis. We believe that our study contributes significantly to the literature because it suggests a novel biomarker for EMs that may facilitate the early diagnosis of the disease without the need for invasive methods such as laparoscopic examination.