D E2F6-miR-193a-EZH2 network could promote stemness of ovarian cancer cells by way of in vitro and in vivo experiments. Ma et al. [9] proved that estrogen promotes the expression of Olfactomedin four (OLFM4) by repressing miR-486-5p in ovarian cancer cells. Furthermore, knockdown of OLFM4 induced proliferation, invasion, and migration of ovarian cancer cells. Xie et al. [10] confirmed that the combined use of estrogen and progesterone promoted expression of let-7a and miR-34b and reduced B-cell lymphoma 2 (Bcl-2) in ovarian cancer cells, major to inhibition of survival and promotion of apoptosis of ovarian cancer cells. When using miRNA inhibitors to suppress endogenous expression of let7a and miR-34b, the combination of estrogen and progesterone did not change the protein amount of Bcl-2 in ovarian cancer cells, suggesting that microRNA let-7a and miR-34b play essential roles inside the clinical remedy of ovarian cancer applying estrogen and progesterone replacement therapy. Estrogen receptor alpha (ER) is often a direct target of miR-206 [11]. Li et al. [12] showed a considerable reduction of miR-206 in ER+ ovarian cancer tissue in comparison with regular ovarian epithelial tissue. Further experiments have shown that estrogen-dependent oncogenic effects in two ovarian cancer cell lines, CAVO-3 and BG-1, might be reversed by introducing miR-206 mimics in ER+ovarian cancer cells. A series of research by the Lim group located that estrogen promotes the expression of 3 oncogenes, Wnt family members member four (Wnt4), avian Caspase 12 Formulation beta-defensin 11 (AvBD-11), and secreted phosphoprotein 1 (SPP1), in hen fallopian tubes. Accordingly, three miRNAs (miR-1786, miR-1615, and miR-140) directly inhibited the expression of those 3 oncogenes [135]. Further research showed that WNT4, AvBD-11, and SPP1 have been expressed in the epithelial glands of cancerous ovaries but downregulated or were not expressed in typical hen ovarian cells. ese benefits recommend that several miRNAs repress estrogen-dependent ovarian cancer by means of targeting of different oncogenes, offering new prospective targets and tips for indepth investigation that may possibly bring about clinical treatments of ovarian cancer. ese miRNA dysfunctions play a part inside the molecular pathogenesis of estrogen-induced ovarian cancer,two. Role of ncRNAs in Estrogen-Dependent Female Reproductive System Tumors2.1. Ovarian Cancer. e oncogenic effects of estrogen are mediated through each receptor-dependent and non-receptordependent manners [1]. Within the receptor-dependent approach, estrogen binds to the nuclear estrogen receptor and causes transcription activation in the estrogen response genes, delivering a signaling cascade for cell division and differentiation. ese genes include numerous key oncogenes, including c-fox, c-myc, and HER2/neu, at the same time as cell-cycle regulatory proteins and development aspects [2]. e binding in between estrogen and membrane-binding G-protein-coupled estrogen receptors (GPER) activates the second messenger system. Consequently, estrogen exerts a quickly, nongenomic impact by way of GPER. e second mechanism is nonreceptor-dependent, and the formation of reactive metabolites via cytochrome P450 enzyme (CYP) might result in the generation of DNA mutation compounds. Totally free radicals developed by estrogen metabolism also can cause mutations, which in turn lead to the accumulation of mutations in many genes inside the fallopian tubes and ovarian cells. is can lead to tumor-like transformation of cells. Nevertheless, all these functions of estrogen are based on coding genes. To further BACE1 Storage & Stability invest.
