Integrated analysis identified novel miRNAs and mRNA in endometriosis.

Abstract

Endometriosis is a common gynecological disease that seriously affects women's health and quality of life. However, the pathogenesis of endometriosis remains uncertain. This study aims to find the key microRNAs (miRNAs) and mRNAs and further to elucidate the pathogenesis of endometriosis. Differentially expressed mRNAs (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs) were obtained by Gene Expression Omnibus (GEO) datasets integration analysis. Functional enrichment analysis of DEmRNAs and DEmRNAs targeted by DEmiRNAs was enforced using GeneCodis3. The DEmiRNA-DEmRNA interaction network was built using Cytoscape. The expression of candidate DEmRNA and DEmiRNA was verified using quantitative real time-polymerase chain reaction (QRT-PCR) and online datasets followed by diagnostic and immune cell infiltration analysis. A total of 835 (327 down-regulated and 508 up-regulated) DEmRNAs and 39 (24 down-regulated and 15 up-regulated) DEmiRNAs were identified between ectopic endometria (EC) group and eutopic endometria (EU) group. DEmRNAs targeted by DEmiRNAs were markedly enriched in cell adhesion molecules, pathways in cancer, leukocyte transendothelial migration, cytokine-cytokine receptor interaction and MAPK signaling pathway. The DEmiRNA-DEmRNA interaction network of up-regulated miRNAs was consisted of 15 miRNAs and 188 corresponding mRNAs. For down-regulated miRNAs, the DEmiRNA-DEmRNA interaction network was consisted of 24 miRNAs and 305 corresponding mRNAs. QRT-PCR validation results of IRF6, PTGER3, NTRK2, hsa-miR-449a and hsa-miR-873-5p were in line with the GEO analysis result. RF6, PTGER3 and NTRK2 had a potential diagnostic value for endometriosis. In addition, the infiltration of macrophages M2 and NK cells activated was the most significantly increased and reduced in ectopic endometrial, respectively. These identified DEmRNAs and DEmiRNAs may be may be associated with the pathogenesis of endometriosis. The integrated analysis of miRNA and mRNA expression profiles may provide a new perspective for understanding the mechanisms of endometriosis and developing new treatments.