Synthetic Steroid Hormones Regulated Cell Proliferation Through MicroRNA-34a-5p in Human Ovarian Endometrioma1

Chia-Yi Hsu, Chia‐Yi Hsu, Tsung‐Hua Hsieh, Tsung-Hua Hsieh, Cheng‐Fang Tsai, Cheng-Fang Tsai, Hung‐Sheng Chen, Hung-Sheng Chen, Peir-In Liang, Peir‐In Liang, Ya-Ling Hsu, Ya‐Ling Hsu, Eing‐Mei Tsai, Eing-Mei Tsai
Biology of reproduction · 2016 · vol. 94(3) · doi:10.1095/biolreprod.115.133330 · W2280260804
article OA: closed CC0 ⤵ 3 in-corpus citations
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Synthetic steroid hormones (danazol, progesterone, MPA) increased miR-34a-5p and miR-199a-5p expression in ovarian endometrioma cells, and inhibiting miR-34a-5p reduced hormone-induced cell proliferation.

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Abstract

Endometriosis is the hormone-dependent product of endometrial tissue found outside the uterus. Recently, micro-RNAs (miRNAs) were shown to play a role in endometriotic lesion development. However, the mechanism of steroid hormones responsible for miRNA remains obscure. In the present study, we assayed for the effects of synthetic steroid hormones (danazol, progesterone, and medroxyprogesterone acetate [MPA]) on miRNAs in endometriosis. We used a global miRNA expression profile microarray to evaluate miRNA expression in endometrial mesenchymal stem cells (EN-MSCs) of ovarian endometrioma following treatment with 1 μM danazol, progesterone, or MPA. Furthermore, we selected candidate miRNAs whose expression changed more than fivefold and compared the effects of danazol, progesterone, and MPA treatments and also compared those results with controls in EN-MSCs. Among those with a fivefold change, we found 13 ectopically upregulated miRNAs in EN-MSCs. To understand the function of these 13 miRNAs, we subjected their sequences to Ingenuity Pathway Analysis. According to both the etiology and pathogenesis of endometriosis, we found that miR-199a-5p and miR-34a-5p showed specific association with the disease, including molecular and cellular functions. Steroid hormone treatment elevated the levels of miR-199a-5p and miR-34a-5p. An inhibitor of miR-34a-5p also reduced the synthetic steroid hormones effects on cell proliferation. In vivo data revealed that miRNA levels in endometriotic lesions correlated with findings following in vitro synthetic hormone treatment. Our data show the effects of synthetic steroid hormones on miRNA regulation. These findings contribute to our understanding of the molecular impact of the synthetic steroid hormones and suggest a potential mechanism for endometriosis treatment.

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Condition tags

mesh:D004715endometriosisendometrioma

MeSH descriptors

Cell Proliferation Endometriosis Gene Expression Regulation MicroRNAs Ovarian Diseases Animals Cell Proliferation Cells, Cultured Cell Survival Danazol Danazol Endometriosis Estradiol Estradiol Female Gene Expression Regulation Gene Expression Regulation Humans Medroxyprogesterone Acetate Medroxyprogesterone Acetate

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