{"paper_id":"b368aedc-f852-43df-a9ee-20faf929a553","body_text":"Abstract\ncircRNAs (circular RNAs) play important roles in the development of endometriosis. This study aimed to explore the functions of circRNAs on endometriosis. Two ectopic, two paired eutopic, and two normal endometrial tissue samples were collected for RNA-seq to obtain circRNA profiles and construct a circRNA–miRNA–mRNA network. The validation of 9 circRNAs in 15 patients was assessed by qRT-PCR. We selected hsa_circ_0008433 as the potential biomarker, followed by examining cell proliferation, colony formation, migration, angiopoiesis, cell cycle, and apoptosis. Furthermore, the expression of apoptosis-related proteins was detected using immunofluorescence (IF) and Western blotting. Bioinformatic analysis was used to select the potential target miRNA and genes of hsa_circ_0008433. A total of 209 upregulated and 117 downregulated differentially expressed circRNAs were identified from the eutopic and ectopic endometrial tissue samples. Eight circRNA levels were significantly increased in ectopic endometrial tissue sample compared with eutopic endometrial tissue. The hsa_circ_0008433 knockdown inhibited endometrial stromal cell proliferation, migration, colony formation, and angiopoiesis; promoted cell apoptosis; and downregulated Ki67 and PCNA expression levels. Moreover, the hsa_circ_0008433 knockdown increased Bax and E-CAD expression and decreased Bcl2, CDKN1B, and CyclinD1 levels. Ten potential target miRNAs of hsa_circ_0008433 were selected, and six of them occur significantly aberrant in hsa_circ_0008433-expressing cells. Increased hsa_circ_0008433 levels regulate epithelial mesenchymal transition (EMT) in endometriosis through the circRNA–miRNA–mRNA axis.\nSimilar content being viewed by others\nData Availability\nThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\nReferences\nBurney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–9. https://doi.org/10.1016/j.fertnstert.2012.06.029.\nSoliman AM, Yang H, Du EX, Kelley C, Winkel C. The direct and indirect costs associated with endometriosis: a systematic literature review. Hum Reprod. 2016;31(4):712–22. https://doi.org/10.1093/humrep/dev335.\nMenakaya U, Infante F, Condous G. Consensus on current management of endometriosis. Hum Reprod. 2013;28(11):3162–3. https://doi.org/10.1093/humrep/det346.\nWang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, et al. 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J Exp Clin Cancer Res. 2019;38(1):169. https://doi.org/10.1186/s13046-019-1136-9.\nCode Availability\nNot applicable.\nAuthor information\nAuthors and Affiliations\nContributions\nHS conceived and designed the study, and critically revised the manuscript. NJ performed the experiments, analyzed the data, and drafted the manuscript. WP, JL, and TC participated in study design, study implementation, and manuscript revision. All authors read and approved the final manuscript.\nCorresponding author\nEthics declarations\nConflict of Interest\nThe authors declare that they have no conflict of interest.\nEthical Approval\nThe study was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-Sen University.\nConsent to Participate\nAll the participants provided written informed consent before recruitment.\nConsent for Publication\nPatients signed informed consent regarding publishing their data and photographs.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nElectronic supplementary material\nESM 1\ncircRNA cyclization sites of eight candidate circRNA verification by Sanger sequencing. Detection of eight candidate circRNAs using gel electrophoresis. (PNG 246 kb)\nRights and permissions\nAbout this article\nCite this article\nJiang, N., Pan, W., Li, J. et al. Upregulated Circular RNA hsa_circ_0008433 Regulates Pathogenesis in Endometriosis Via miRNA. Reprod. Sci. 27, 2002–2017 (2020). https://doi.org/10.1007/s43032-020-00219-1\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-020-00219-1","source_license":"CC0","license_restricted":false}