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

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.

• Authors: Chia-Yi Hsu, Tsung-Hua Hsieh, Cheng-Fang Tsai, Hung-Sheng Chen, Peir-In Liang, Ya-Ling Hsu, Eing-Mei Tsai
• Journal: Biology of reproduction (Biol Reprod) Vol. 94 Issue 3 Pg. 60 (Mar 2016) ISSN: 1529-7268 [Electronic] United States
• PMID: 26819477 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by the Society for the Study of Reproduction, Inc.

Chemical References

• MicroRNAs
• NOTCH1 protein, human
• Notch1 protein, mouse
• Receptor, Notch1
• Progesterone
• Estradiol
• Medroxyprogesterone Acetate
• Danazol

Topics

• Animals
• Cell Proliferation (drug effects)
• Cell Survival
• Cells, Cultured
• Danazol (pharmacology)
• Endometriosis (metabolism)
• Estradiol (pharmacology)
• Female
• Gene Expression Regulation (drug effects, physiology)
• Humans
• Medroxyprogesterone Acetate (pharmacology)
• Mice
• MicroRNAs (genetics, metabolism)
• Ovarian Diseases (metabolism)
• Progesterone (pharmacology)
• Receptor, Notch1
• Transcriptome
• Up-Regulation (drug effects)