MiR-199a attenuates endometrial stromal cell invasiveness through suppression of the IKK /NF- B pathway and reduced interleukin-8 expression

Lan Dai, Liankun Gu, Liying Gu, Wen Di
Molecular human reproduction · 2011 · vol. 18(3) , pp. 136–145 · doi:10.1093/molehr/gar066 · PMID:21989168 · PMC3292395 · W2125281291
article OA: bronze CC0 ⤵ 42 in-corpus citations
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This study found that miR-199a, which is downregulated in endometriosis, suppresses endometrial stromal cell invasiveness by inhibiting the IKK/NF-κB pathway and reducing interleukin-8 expression.

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Abstract

MicroRNAs have recently been identified as regulators that modulate target gene expression and are suggested to be involved in the development and progression of endometriosis. This study was undertaken to analyze the expression level of microRNA-199a (miR-199a) in paired ovarian endometrioma and eutopic endometrium from women with endometriosis, and to investigate the contribution of miR-199a to the invasive capability of endometrial stromal cells (ESCs). Cell adhesion, migration and Matrigel invasion assays were carried out to measure the invasiveness of ESCs. Bioinformatics prediction, reporter gene assay, PCR, western blotting and ELISA were performed to identify miR-199a targets and related signaling pathways. The results showed that the expression level of miR-199a was lower in the eutopic endometrium from women with endometriosis, and even lower in the paired ovarian endometrioma, compared with the expression in normal controls. Moreover, ectopic expression of miR-199a attenuated ESC adhesion, migration and invasiveness. MiR-199a targeted and inhibited IkappaB kinase beta (IKKβ) in ESCs. Accompanied by IKKβ reduction, miR-199a suppressed nuclear factor-kappa B (NF-κB) pathway activation and interleukin-8 (IL-8) production in ESCs. All these findings suggest that miR-199a, down-regulated in endometriosis, attenuates the invasive capability of ESCs in vitro partly through IKK/NF-κB pathway suppression and reduced IL-8 expression. In conclusion, miR-199a could be involved in the pathogenesis of endometriosis.

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Condition tags

endometriosisendometrioma

MeSH descriptors

Endometrium I-kappa B Kinase Interleukin-8 MicroRNAs NF-kappa B Stromal Cells Stromal Cells Adult Blotting, Western Cell Adhesion Cell Adhesion Cell Adhesion Cell Movement Cell Movement Cell Movement Cells, Cultured Endometriosis Endometriosis Endometrium Enzyme-Linked Immunosorbent Assay

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