miR-34a-5p 和miR-199a-5p在子宮內膜異位症發展過程中所扮演的角色

Endometriosis is the hormone-dependent disease that the presence of endometrium-like tissue in sites outside the uterine. Recent research has shown that miRNAs play a role in endometrial lesion development. Aim 1. The mechanism of steroid hormones responsible for miRNA, however, remains obscure. Our objective was to assess the effects of synthetic steroid hormones (danazol, progesterone, and medroxyprogesterone acetate (MPA)) on miRNAs in endometriosis. First, the expression profile miRNA of synthetic steroid homorne treatment by using a global miRNA microarray and then Ingenuity Pathway Analysis (IPA) software was used to select candidate miRNA whose expression was changed by more than five-fold by synthetic steroid homorne compared with controls to analyze the bio-functions in EN-MSCs Among those with a five-fold change, 13 ectopically upregulated miRNAs were found in EN-MSCs. According to both the etiology and pathogenesis of endometriosis, miR-199a-5p and miR-34a-5p showed specific association with the disease, including molecular and cellular functions. Synthetic steroid hormone treatment elevated the levels of miR-199a-5p and miR-34a-5p. An inhibitor of miR-34a-5p also reduced synthetic steroid hormone effects on cell proliferation. Furthermore, miRNA levels in endometrial lesions in an animal model of endometriosis were correlated with findings following in vitro synthetic hormone treatment. These data show the effects of synthetic steroid hormones on miRNA regulation. Aim 2. How endometrial miRNAs contribute to the etiology of endometriosis in stem cells, however, remains unclear. The miRNA expression profiles were characterized from serum samples of patients with or without endometriosis. MicroRNA-199a-5p (miR-199a-5p) was dramatically down-regulated in patients with endometriosis compared with control patients. In addition, tumor suppressor gene, SMAD4, could elevate miR-199a-5p expression in ectopic EN-MSCs. Restoration of miR-199a-5p expression in ectopic EN-MSCs reduecs cell proliferation, motility, and angiogenesis by targeting the 3' untranslated region of VEGFA. In vivo data revealed that miR-199a-5p could decrease the size of endometriotic lesions. These findings contribute to identify miR-199a-5p module provides a new avenue to the understanding of the processes of endometriosis development, especially proliferation, motility as well as angiogenesis. Taken together, our understanding of the molecular impact of the synthetic steroid hormones and suggest a potential mechanism for endometriosis treatment and may facilitate the development of potential therapeutics against endometriosis.