miR-769-5p inhibits cellular behaviors associated with endometriosis progression by directly targeting follistatin in vitro

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miR-769-5p is downregulated in endometriosis serum and targets follistatin to inhibit the proliferation, migration, and invasion of ectopic endometrial stromal cells in vitro.

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This study investigated microRNA-769-5p (miR-769-5p) in endometriosis using serum from 120 endometriosis patients and 100 healthy controls, along with functional assays in an endometriosis-derived stromal cell line (hEM15A). miR-769-5p was markedly downregulated in endometriosis sera and was inversely correlated with disease severity, with diagnostic accuracy reported by RT-qPCR (AUC = 0.9166). In vitro, miR-769-5p overexpression suppressed proliferation, migration, and invasion of hEM15A cells, and mechanistically it targeted follistatin (FST), with FST overexpression partially reversing these inhibitory effects. This paper directly relates to endometriosis—miR-769-5p downregulation and its FST-targeting mechanism were tested in an endometriosis stromal cell model to inhibit progression-associated cellular behaviors.

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Abstract

The pathogenesis of endometriosis (EM) remains intricate and multifactorial. This study aimed to investigate the biological functions of microRNA-769-5p (miR-769-5p) in an in vitro model of EM. Serum was obtained from 120 EM patients and 100 healthy controls. miRNA and mRNA expression were quantified by RT-qPCR. Functional analyses of miR-769-5p were performed in vitrousing cell counting kit-8 (CCK-8) cell proliferation assays, Transwell assays, and dual-luciferase assays in an endometriosis-derived stromal cell line (hEM15A). miR-769-5p was markedly down-regulated in EM sera and correlated inversely with disease severity (p < 0.001). Moreover, miR-769-5p exhibited high diagnostic accuracy for EM (AUC = 0.9166, p < 0.001). In the hEM15A cell model, overexpression of miR-769-5p effectively suppressed the proliferation, migration, and invasion capabilities of EM-derived stromal cells (p < 0.001). miR-769-5p targeted follistatin (FST) and negatively regulated its expression in vitro (p < 0.001). In contrast, FST overexpression could partially reverse the inhibitory effects of miR-769-5p-mimic on these EM-derived cells. Our findings indicate that miR-769-5p is downregulated in EM serum. Furthermore, in vitro experiments suggest that it can target FST to inhibit proliferation, migration, and invasion of ectopic endometrial stromal cells.
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Abstract

The pathogenesis of endometriosis (EM) remains intricate and multifactorial. This study aimed to investigate the biological functions of microRNA-769-5p (miR-769-5p) in an in vitro model of EM. Serum was obtained from 120 EM patients and 100 healthy controls. miRNA and mRNA expression were quantified by RT-qPCR. Functional analyses of miR-769-5p were performed in vitrousing cell counting kit-8 (CCK-8) cell proliferation assays, Transwell assays, and dual-luciferase assays in an endometriosis-derived stromal cell line (hEM15A). miR-769-5p was markedly down-regulated in EM sera and correlated inversely with disease severity (p < 0.001). Moreover, miR-769-5p exhibited high diagnostic accuracy for EM (AUC = 0.9166, p < 0.001). In the hEM15A cell model, overexpression of miR-769-5p effectively suppressed the proliferation, migration, and invasion capabilities of EM-derived stromal cells (p < 0.001). miR-769-5p targeted follistatin (FST) and negatively regulated its expression in vitro (p < 0.001). In contrast, FST overexpression could partially reverse the inhibitory effects of miR-769-5p-mimic on these EM-derived cells. Our findings indicate that miR-769-5p is downregulated in EM serum. Furthermore, in vitro experiments suggest that it can target FST to inhibit proliferation, migration, and invasion of ectopic endometrial stromal cells.

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Disclosure statement No potential conflict of interest was reported by the authors. Data availability statement The original qPCR Ct table, luciferase values and other raw data have been presented as Supplementary Table 1. Further enquiries can be directed to the corresponding author.

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endometriosis

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