Abstract
BackgroundThe etiology and pathophysiology of endometriosis remain unclear. Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis. This study therefore aims to survey the key miRNAs, TFs and genes and further understand the mechanism of endometriosis.MethodsPaired expression profiling of miRNA and mRNA in ectopic endometria compared with eutopic endometria were determined by high-throughput sequencing techniques in eight patients with ovarian endometriosis. Binary interactions and circuits among the miRNAs, TFs, and corresponding genes were identified by the Pearson correlation coefficients. miRNA-TF-gene regulatory networks were constructed using bioinformatic methods. Eleven selected miRNAs and TFs were validated by quantitative reverse transcription-polymerase chain reaction in 22 patients.ResultsOverall, 107 differentially expressed miRNAs and 6112 differentially expressed mRNAs were identified by comparing the sequencing of the ectopic endometrium group and the eutopic endometrium group. The miRNA-TF-gene regulatory network consists of 22 miRNAs, 12 TFs and 430 corresponding genes. Specifically, some key regulators from the miR-449 and miR-34b/c cluster, miR-200 family, miR-106a-363 cluster, miR-182/183, FOX family, GATA family, and E2F family as well as CEBPA, SOX9 and HNF4A were suggested to play vital regulatory roles in the pathogenesis of endometriosis.ConclusionIntegration analysis of the miRNA and mRNA expression profiles presents a unique insight into the regulatory network of this enigmatic disorder and possibly provides clues regarding replacement therapy for endometriosis.
Highlights
IntroductionAccumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis
The etiology and pathophysiology of endometriosis remain unclear
The miRNA expression levels can be regulated by transcription factor (TF), and the messenger RNA (mRNA) encoding TFs can be inhibited by miRNAs [10]
Summary
Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis. Zhao et al Reproductive Biology and Endocrinology (2018) 16:4 expression at the post-transcriptional level [5]. They negatively regulate the translation of target messenger RNAs (mRNAs) via the sequence specific recognition of the “seed sequence” and repress translation and/or degrade the target mRNAs according to the degree of complementary nucleotides [6]. Transcription factors (TFs) are a group of proteins that regulate gene expression by binding to specific DNA sequences at the transcriptional level [7]. The combinatorial regulation of TFs and miRNAs is suggested to play vital roles in various biological processes and disease pathogenesis [12,13,14,15]
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