Upregulated Circular RNA hsa_circ_0008433 Regulates Pathogenesis in Endometriosis Via miRNA
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ORIGINAL ARTICLE
Upregulated Circular RNA hsa_circ_0008433 Regulates Pathogenesis in Endometriosis Via miRNA Nan Jiang 1 & Wenwei Pan 1 & Jinhui Li 1 & Tiefeng Cao 1 & Huimin Shen 1 Received: 23 March 2020 / Accepted: 18 May 2020 # Society for Reproductive Investigation 2020
Abstract circRNAs (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 apoptosisrelated 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. Keywords Endometriosis . circRNA . EMT . miRNA . hsa_circ_0008433
Introduction Endometriosis is a gynecologic disease characterized by uterine epithelial presence and stromal tissues outside of the uterine cavity [1]. It has been reported to occur in about 10% of reproductive-age women, with a peak in those aged 25– 35 years [1, 2]. Over 176 million women suffer from endometriosis-associated pain and infertility worldwide [3]. This disease also imposes a considerable economic burden on society. There is no proper sensitive and specific biomarker for endometriosis patients. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43032-020-00219-1) contains supplementary material, which is available to authorized users. * Huimin Shen [email protected] 1
The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Second Road, Guangzhou 510080, Guangdong, China
circRNAs (circular RNAs) are a type of noncoding RNA that can absorb miRNAs (microRNAs) and enhance mRNA translation, having important roles in gene regulation [4]. circRNA
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