microRNAs expression in endometriosis and their relation to angiogenic factors

Luis A Ramón, Luis Ramón, Aitana Braza-Boïls, Aitana Braza‐Boïls, Juan Gilabert–Estellés, Juan Gilabert-Estellés, Juan Gilabert, J. Gilabert, Francisco España, Melitina Chirivella, M. Chirivella, A. Estellés, Amparo Estellés
Human Reproduction · 2011 · vol. 26(5) , pp. 1082–1090 · doi:10.1093/humrep/der025 · PMID:21335415 · W2127311828
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Endometriotic lesions showed altered expression of angiogenesis-related microRNAs and factors compared to eutopic endometrium, with specific inverse correlations noted between miR-222 and VEGF-A, and miR-17-5p and TSP-1.

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Abstract

BACKGROUND: Endometriosis is a common, multifactorial disease in which angiogenesis may be involved in the growth of endometrium outside the uterus. microRNAs (miRNAs) are 21-22 nucleotide non-coding RNAs that regulate gene expression and play fundamental roles in biological processes. The objective of this study was to analyze several miRNAs related to angiogenesis and the angiogenic factors, vascular endothelial growth factor-A (VEGF-A) and thrombospondin-1 (TSP-1), in endometriotic lesions (ovarian endometrioma, peritoneal lesion and rectovaginal nodule) and eutopic endometrium from women with endometriosis. METHODS: TaqMan real-time PCR was used to assess the expression of the miRNAs (miR-15b, -16, -17-5p, -20a, -21, -125a, -221 and -222), while VEGF-A and TSP-1 mRNA were assessed by real-time PCR, with SYBR Green I and VEGF-A and TSP-1 protein levels were quantified by ELISA. Included in the study were 58 women with endometriosis and 38 control women. RESULTS: In paired samples, ovarian endometrioma showed significantly lower VEGF-A mRNA (P = 0.02) and protein (P = 0.002) expression than eutopic endometrium and higher expression of miR-125a (P = 0.003) and miR-222 (P <0.001). However, ovarian endometrioma had significantly higher expression of the angiogenic inhibitor TSP-1 and lower expression of miR-17-5p than eutopic endometrium (P < 0.001). Moreover, a significant inverse correlations between miR-222 and VEGF-A protein levels (-0.267, P = 0.018) and between miR-17-5p and TSP-1 protein levels (-0.260, P=0.022) were observed. Peritoneal lesions showed a significant increase in VEGF-A in comparison with ovarian endometrioma (P < 0.01). CONCLUSIONS: Expression levels of miRNAs related to angiogenesis were different in eutopic endometrium from that observed in ovarian endometrioma. This could influence the expression of angiogenic factors and play a role in the pathogenesis of endometriosis.

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Condition tags

mesh:D004715endometriosisendometrioma

MeSH descriptors

Angiogenesis Inducing Agents Endometriosis MicroRNAs Adult Angiogenesis Inducing Agents Endometriosis Endometriosis Enzyme-Linked Immunosorbent Assay Female Gene Expression Regulation Humans Menstrual Cycle Menstrual Cycle Menstrual Cycle MicroRNAs Neovascularization, Pathologic Neovascularization, Pathologic Neovascularization, Pathologic RNA, Messenger Thrombospondin 1

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