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MiR-182 inhibits proliferation, migration, invasion and inflammation of endometrial stromal cells through deactivation of NF-κB signaling pathway in endometriosis

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Abstract

Endometriosis affects about 10-15% women for reproductive age, but it is not currently curable and the underlying etiology for this disease is still not clear. In the present study, functions and mechanisms of miR-182 and RELA in endometriosis were investigated. BAY 11-7082 was used to block NF-κB pathway. qRT-PCR, ELISA and western blot assays were employed to evaluate the expressions of miR-182 and RELA, inflammatory factors and epithelial–mesenchymal transition (EMT)-related markers, and activation of NF-κB pathway. MTT, wound healing or Transwell assays were used to evaluate the cell proliferation, migration and invasion capacities. Bioinformatic and dual-luciferase reporter assays were carried out to analyze the interaction between miR-182 and RELA. MiR-182 expression was decreased, while RELA was increased as developed from normal to eutopic and ectopic status, which was accompanied by upregulated inflammatory factors and EMT-related proteins. RELA was directly targeted by miR-182 in human endometrial stromal cells. Overexpression of RELA increased inflammation-associated and EMT-related markers expression, while miR-182 upregulation decreased the expression of these genes in a dose-dependent manner, which finally attenuated the proliferation, migration and invasion capacities of endometrial stromal cells through deactivation of NF-κB signaling pathway. Moreover, co-overexpression of RELA reversed the above effects induced by miR-182. In a word, miR-182 directly targeted RELA and inhibited proliferation, migration, invasion, EMT and inflammation of endometrial stromal cells through deactivation of NF-κB signaling pathway in endometriosis. These results provide new insights into the interaction between miR-182 and NF-κB pathway and their potential as therapeutic targets for treatment of endometriosis.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the grant from Health Commission of Hunan Province (No. B2017125).

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, People’s Republic of China

    Min Wu & Yi Zhang

  2. Department of Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, Hunan Province, People’s Republic of China

    Min Wu

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  1. Min Wu
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Contributions

Guarantor of integrity of the entire study: MW. Study concepts: MW. Study design: YZ. Definition of intellectual content: MW. Literature research: MW. Clinical studies: MW. Experimental studies: MW. Data acquisition: MW. Data analysis: MW. Statistical analysis: MW. Manuscript preparation: MW. Manuscript editing: MW. Manuscript review: YZ. All the authors approved for the final version.

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Correspondence to Yi Zhang.

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The authors declare that they have no conflict of interest.

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This study has been conducted strictly following the ethical standards of Ethics Committee of Hunan Provincial Maternal and Child Health Care Hospital (Changsha, Hunan, China). Written informed consent was obtained from each patient and healthy participant before the collection of any specimen.

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Wu, M., Zhang, Y. MiR-182 inhibits proliferation, migration, invasion and inflammation of endometrial stromal cells through deactivation of NF-κB signaling pathway in endometriosis. Mol Cell Biochem 476, 1575–1588 (2021). https://doi.org/10.1007/s11010-020-03986-2

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  • DOI: https://doi.org/10.1007/s11010-020-03986-2

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