Expression Profile Analysis of Circular RNAs in Ovarian Endometriosis by Microarray and Bioinformatics

Abstract

BackgroundEndometriosis is a common gynecologic disorder with enigmatic etiopathogenesis and is characterized by tumor-like biological behaviors. Recently, circular RNAs (circRNAs) have attracted considerable attention because they exert very important functions in the progression of human cancers. However, little is known about the functions and molecular mechanism of circRNAs in endometriosis.Material/MethodsA total of 20 patients with ovarian endometriosis and 4 normal endometrium from women free of endometriosis were included in this study. Ectopic endometrium tissues and paired eutopic endometrium tissues were collected from ovarian endometriosis patients. We assessed the expression profiles of circRNAs in endometriosis by microarray analysis. Expression of selected circRNAs in those tissues was detected by quantitative real-time PCR (qRT-PCR). Based on the target prediction, we constructed a circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network and elucidated circRNAs through Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses.ResultsWe detected 2237 circRNAs, differentially expressed among 3 groups, and then found 8 circRNAs that may be involved in the epithelial-mesenchymal transition process. The qRT-PCR validation suggested that circ_103470 and circ_101102 matched the microarray results. The functional analysis revealed 17 pathways, such as the mTOR signaling pathway, the Hippo signaling pathway, and the HIF-1 signaling pathway, which may be associated with the pathogenesis and development of endometriosis.ConclusionsIn general, our results suggest that 2 downregulated circRNAs (circ_103470 and circ_101102) may regulated epithelial-mesenchymal transition in endometriosis via miR-141-5p, which may be a promising therapeutic target in the future.

Circular RNA expression profiles and bioinformatics analysis in ovarian endometriosis

“…In this study, we investigated circRNA expression profiles in ecEM compared with euEM of endometriosis patients and identified 294 differentially expressed circRNAs, 146 upregulated and 148 downregulated. Most of those dysregulated circRNAs originate from exons or introns which are in accordance with previous researches (Shen et al, ; Xu et al, , ; Zhang, Ren, Xiao, Xia, & Fang, ). It has been reported that both exonic and intronic circRNAs may exert potential functions in gene regulation (Greene et al, ).…”

“…Xu et al () revealed for the first time the circRNA expression patterns between women with and without endometriosis and found that the increased level of circ_0004712 and circ_0002198 could help identify the patients with endometriosis. Zhang, Ren, et al () assessed the expression profiles of circRNAs in endometriosis by microarray analysis and detected 2,237 circRNAs differentially expressed among ectopic endometrium (EC) (endometriotic lesions), paired eutopic endometrium (EU), and normal endometrium from women free of endometriosis, and qRT‐PCR validation suggested that downregulated circ_103470 and circ_101102 matched the microarray results. In our study, four of nine upregulated circRNAs (hsa_circ_0003380, hsa_circ_0020093，hsa_circ_0008016 and hsa_circ_0077837) were confirmed by qRT‐PCR, which was consistent with sequence assays.…”

Comprehensive analysis of mRNAs and miRNAs in the ovarian follicles of uniparous and multiple goats at estrus phase

“…miR-200a was frequently overexpressed and is closely related to the migratory, proliferative, and invasive abilities of OC cells [80][81][82]. miR-141 was shown to be significantly upregulated in OC cell lines and advanced metastatic OC [83,84], and can inhibit GC apoptosis by targeting DAPK1 through the MAPK signaling pathway, leading to the development of polycystic ovary syndrome (PCOS) [85]. In this study, miR-200a and miR-141 expression were upregulated in the small follicles of uniparous goats, suggesting that these miRNAs might affect normal GC development, thereby affecting follicular development.…”

Circ_0007331 knock‐down suppresses the progression of endometriosis via miR‐200c‐3p/HiF‐1α axis

“…Analysis of clinical samples by microarray and bioinformatics methods revealed 88 differentially expressed circRNAs between eutopic and normal endometrium, of which 11 were up‐regulated and 77 were down‐regulated 12 . In addition, circ_103470 and circ_101102 were found to regulate epithelial‐mesenchymal transition (EMT) of endometriosis through sponge miR‐141‐5p 13 . Further functional analysis showed that downstream mRNAs of these differentially expressed circRNAs are mainly involved in immune‐inflammatory response and cell cycle regulation.…”