Role of miR‑139‑5p in ectopic endometrial stromal cells and the underlying molecular mechanism

Feng,Lixia; Chen,Xu; Zhang,Shenghua; Chen,Yunxia; Yu,Yanling

doi:10.3892/etm.2021.10686

Role of miR‑139‑5p in ectopic endometrial stromal cells and the underlying molecular mechanism

Authors:
- Lixia Feng
- Xu Chen
- Shenghua Zhang
- Yunxia Chen
- Yanling Yu
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Affiliations: Department of Gynecology, The Second Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518100, P.R. China, Department of Obstetrics and Gynecology, Huashan Hospital North Affiliated to Fudan University, Shanghai 210907, P.R. China, Department of Obstetrics and Gynecology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China
Published online on: September 2, 2021 https://doi.org/10.3892/etm.2021.10686
Article Number: 1251
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometriosis is an estrogen‑dependent disease. Studies have shown that miR‑139‑5p is significantly upregulated in endometriosis lesions, but its specific role and molecule mechanism in endometriosis has not yet been reported. The malignant biological behavior of ectopic endometrial stromal cells (ESCs) is similar to that of malignant cancer cells. BBC3 (BCL2 binding component 3) is a known apoptosis inducer and it serves key roles in the regulation of cell behavior. However, the role of BBC3 in ectopic ESCs remains unknown. The present study aimed to investigate the role of miR‑139‑5p in the progression of endometriosis and to determine its underlying molecular mechanism of action. Ectopic, non‑ectopic and normal endometrial stromal cells (ESCs) were extracted from endometrial samples, and reverse transcription‑quantitative PCR was performed to determine microRNA (miR)‑139‑5p and Bcl‑2 binding component 3 (BBC3) mRNA expression levels in endometrial tissue samples and ESCs. The target gene of miR‑139‑5p was predicted using TargetScan software and verified using a dual luciferase reporter assay. Western blotting was performed to determine BBC3 protein expression levels. Flow cytometry analysis, and MTT and Transwell assays were performed to assess cell apoptosis, viability, and migration and invasion of the cells transfected with inhibitor control, miR‑139‑5p inhibitor, miR‑139‑5p inhibitor + control‑small interfering (si)RNA or miR‑139‑5p inhibitor + BBC3‑siRNA, respectively. The results demonstrated that miR‑139‑5p expression levels were upregulated in ectopic endometrial samples and ESCs compared with the respective control groups. Furthermore, it was verified that BBC3 was a direct target of miR‑139‑5p, and both BBC3 mRNA and protein expression levels were downregulated in ectopic endometrial samples and ESCs. Both transfection with the miR‑139‑5p inhibitor and BBC3‑small interfering (si)RNA markedly downregulated miR‑139‑5p and BBC3 expression levels in ectopic ESCs, respectively. miR‑139‑5p inhibitor‑induced upregulated BBC3 expression was reversed following transfection with BBC3‑siRNA. Furthermore, the miR‑139‑5p inhibitor significantly decreased viability, migration and invasion, while inducing apoptosis in ectopic ESCs compared with the inhibitor control group. Notably, the aforementioned effects were reversed by knocking down BBC3 expression. In conclusion, the results of the present study suggested that miR‑139‑5p may play a key role in the progression of endometriosis by regulating the viability of ESCs and directly targeting BBC3.

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