miR-45la Inhibition Reduces Established Endometriosis Lesions in Mice

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Inhibition of miR-451a in mice reduced established endometriosis lesion size and altered expression of genes including YWHAZ, CAB39, MAPKI, β-catenin, and IL-6.

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This study tested whether inhibiting microRNA-451a could reduce established endometriosis in a murine model, using a miR-451a inhibitor versus a scrambled microRNA control. Treatment with the miR-451a inhibitor significantly reduced endometriosis lesion size (13 mm3 vs 30 mm3) but did not change the number of visible lesions, and it altered expression of genes including YWHAZ, CAB39, MAPKI, β-catenin, and IL-6. The paper is based on systemic inhibitor delivery in mice and does not report lesion-related functional outcomes beyond size/visible lesion counts. This paper is centrally about endometriosis — it evaluates systemic miR-451a inhibition to reduce established endometriotic lesion size in mice.

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Abstract

Endometriosis is an estrogen-dependent pro-inflammatory disease that affects 6% to 10% of reproductive-age women. Current treatments target sex steroids, and none are disease-specific. MicroRNA treatments have provided promising results for some chronic diseases and cancers. We have previously shown microRNA 451a is increased in endometriosis and that elevation of 451a contributes to the pathophysiology of the disease. Here, we propose inhibition of miR-451a for the treatment of endometriosis in a murine model. Endometriosis was treated using a microRNA 451a inhibitor or a scrambled control microRNA. Treatment with miR-451a inhibitor resulted in reduced endometriosis lesion size (30 vs 13 mm3). There was no difference in the number of visible lesions between the miR-451a treatment and controls. Treatment led to altered expression of several genes including YWHAZ, CAB39, MAPK1, β-catenin, and IL-6. Systemic treatment with a miR-451a inhibitor is a promising therapy for endometriosis that simultaneously affects multiple pathways driving the disease.
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Abstract

Endometriosis is an estrogen-dependent pro-inflammatory disease that affects 6% to 10% of reproductive-age women. Current treatments target sex steroids, and none are disease-specific. MicroRNA treatments have provided promising results for some chronic diseases and cancers. We have previously shown microRNA 451a is increased in endometriosis and that elevation of 451a contributes to the pathophysiology of the disease. Here, we propose inhibition of miR-451a for the treatment of endometriosis in a murine model. Endometriosis was treated using a microRNA 451a inhibitor or a scrambled control microRNA. Treatment with miR-451a inhibitor resulted in reduced endometriosis lesion size (30 vs 13 mm3). There was no difference in the number of visible lesions between the miR-451a treatment and controls. Treatment led to altered expression of several genes including YWHAZ, CAB39, MAPKI, β-catenin, and IL-6. Systemic treatment with a miR-451a inhibitor is a promising therapy for endometriosis that simultaneously affects multiple pathways driving the disease. Similar content being viewed by others

References

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Nothnick WB, Falcone T, Joshi N, Fazleabas AT, Graham A. Serum miR-451a levels are significantly elevated in women with endometriosis and recapitulated in baboons (Papio anubis) with experimentally-induced disease. Reprod Sci. 2017;24(8): 1195–1202. Sahin C, Mamillapalli R, Yi KW, Taylor HS. microRNA Let-7b: a novel treatment for endometriosis. JCellMolMed. 2018;22(11):5346–5353. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Li, M., Zhou, Y. & Taylor, H.S. miR-45la Inhibition Reduces Established Endometriosis Lesions in Mice. Reprod. Sci. 26, 1506–1511 (2019). https://doi.org/10.1177/1933719119862050 Published: Version of record: Issue date: DOI: https://doi.org/10.1177/1933719119862050

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endometriosis

MeSH descriptors

Endometriosis Endometriosis MicroRNAs MicroRNAs Animals Endometriosis Endometriosis Female Mice Mice, Inbred C57BL MicroRNAs MicroRNAs MicroRNAs MicroRNAs

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