Abstract
Objective MicroRNAs play vital roles in the development of endometriosis. It is reported that miR-200b-3p is downregulated in endometriosis, although its mechanisms in this disease remain still unclear. Therefore, the purpose of this study was to explore the function and potential regulatory network of miR-200b-3p in endometriosis through database analysis. Methods The endometriosis gene expression profiles were downloaded from the GEO database to screen differentially expressed genes (DEGs). The predicted and validated target genes of miR-200b-3p were obtained from miRWalk and miRTarBase database. Then, a comparison was performed between miR-200b-3p target genes and DEGs. GO enrichment and KEGG pathway analysis of the target genes was performed using clusterProfiler package. STRING was used to predict the protein-protein interaction among the proteins encoded by the target genes. Then, TransmiR, LncBase, StarBase, PROMO, and AnimalTFDB were employed to identify interactive transcription factors and lncRNAs of miR-200b-3p. Results miR-200b-3p was associated with the transcription factors DNMT1, EZH2, HNF1B, JUN, MYB, ZEB1, and ZEB2 during the pathogenesis of endometriosis. The downstream 110 target genes were involved in the biological processes of positive regulation of MAPK cascade, muscle cell proliferation, organ growth, vasculogenesis, and axon development. KEGG analysis revealed that the main pathways related to miR-200b-3p were microRNAs in cancer, PI3K-Akt signaling pathway, colorectal cancer, and tight junction. In addition, four lncRNAs such as MALAT1, NEAT1, SNHG22, and XIST interacted with miR-200b-3p and were associated with transcription factors FOXP3 and YY1. Conclusion The predicted target genes and molecular regulatory network of miR-200b-3p in endometriosis not only revealed its biological function but also provided a valuable guideline for further research.
Highlights
Endometriosis is a benign gynaecological disease characterized by endometrial glands and stroma located outside the uterine cavity
Previous microarray studies demonstrated that some miRNAs are aberrantly expressed in endometriosis [6,7,8]. miR-200b-3p, one of the miRNAs downregulated in endometriosis [9, 10], belongs to the miR-200 family, and it is involved in the regulating of epithelial-to-mesenchymal transition (EMT) in endometriotic cells [11]
Endometriosis is a benign inflammatory disease, some of its characteristics are comparable to the ones of malignant tumours, such as abnormal cell migration, implantation, invasion, and angiogenesis
Summary
Endometriosis is a benign gynaecological disease characterized by endometrial glands and stroma located outside the uterine cavity. It affects 10–15% of women in their reproductive age and results in a significantly affected quality of life [1, 2]. MicroRNAs (miRNAs) are small, single-strand noncoding RNA molecules containing ~22 nucleotides, which regulate the expression of target genes and control a variety of cellular functions, including apoptosis, proliferation, migration, and invasion [4]. Through a combinatorial action of miRNAs, transcription factors (TFs), and long noncoding RNAs (lncRNAs), more complex regulatory networks are often involved in various biological events [5]. Little is known about the BioMed Research International potential function and regulatory network of miR-200b-3p in endometriotic lesions
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