WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs
Mengxiong Li,1,* Zhi Zeng,2,* Aiqing Zhang,3 Qingjian Ye,4 Shujun Su,4 Tingting Xia5 1Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, People’s Republic of China; 2The Department of Reproductive Medicine...
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2021
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oai:doaj.org-article:3f4cb9ccbfa54c3ab71541b65560c80b2021-11-23T18:43:01ZWGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs1178-7074https://doaj.org/article/3f4cb9ccbfa54c3ab71541b65560c80b2021-11-01T00:00:00Zhttps://www.dovepress.com/wgcna-analysis-identifies-polycystic-ovary-syndrome-associated-circula-peer-reviewed-fulltext-article-IJGMhttps://doaj.org/toc/1178-7074Mengxiong Li,1,* Zhi Zeng,2,* Aiqing Zhang,3 Qingjian Ye,4 Shujun Su,4 Tingting Xia5 1Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, People’s Republic of China; 2The Department of Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 5Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tingting Xia Tel +86-020-85256032Email xiatting@mail.sysu.edu.cnObjective: Dysfunction of cumulus granulosa cells has been suggested as a contributor to abnormal folliculogenesis and the development of polycystic ovary syndrome (PCOS), but the underlying molecular mechanisms remain unclear. Recent studies indicate that circular RNAs (circRNAs) exert important roles for diseases. We aimed to screen crucial circRNAs of PCOS patients and predict their functions.Methods: The high-throughput datasets of circRNAs (GSE145296), microRNAs (miRNAs; GSE72274) and messenger RNAs (mRNAs; GSE155489) in cumulus cells of PCOS patients and controls were collected from the Gene Expression Omnibus database. Differentially expressed circRNAs (DECs), miRNAs (DEMs) and protein-coding genes (DEGs) were identified by the limma method. The weighted correlation network analysis (WGCNA) was conducted using the DECs to mine PCOS-associated modules. Hub DECs in modules were defined as both of |gene significance| and |module membership| > 0.8. The downstream effectors of hub DECs were predicted by constructing DEC-DEM-DEG ceRNA and DEC-RNA binding protein (RBP) networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of circRNAs.Results: A total of 3614 DECs, 3544 DEGs and 1469 DEMs were identified between PCOS and controls. WGCNA analysis yielded five PCOS-related modules, of which 190 DECs were hub circRNAs. Seventeen hub DECs, nine DEMs, and 315 DEGs were identified to construct the ceRNA network, while 56 hub DECs and two DEGs (MBNL2, RBPMS) constituted the circRNA-RBP network. Five hub DECs (hsa_circ_0063309, hsa_circ_0054275, hsa_circ_0056196, hsa_circ_0018108 and hsa_circ_0070987) were overlapped between ceRNA and DEC-MBNL2 regulatory networks and thus they may be pivotal for PCOS. Furthermore, hsa_circ_0099109 could interact with the RBP gene RBPMS. Function analyses showed these circRNAs were inflammation-, apoptosis- or steroidogenesis-related.Conclusion: Aberrant expression of six circRNAs that function as RBP regulators or miRNA sponges may be possible mechanisms underlying the pathogenesis of PCOS by affecting apoptosis and steroidogenesis in cumulus cells.Keywords: circular RNAs, competitive endogenous RNAs, polycystic ovary syndrome, RNA-binding proteins, weighted gene co-expression network analysisLi MZeng ZZhang AYe QSu SXia TDove Medical Pressarticlecircular rnascompetitive endogenous rnaspolycystic ovary syndromerna binding proteinsweighted gene co-expression network analysis.Medicine (General)R5-920ENInternational Journal of General Medicine, Vol Volume 14, Pp 8737-8751 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
circular rnas competitive endogenous rnas polycystic ovary syndrome rna binding proteins weighted gene co-expression network analysis. Medicine (General) R5-920 |
| spellingShingle |
circular rnas competitive endogenous rnas polycystic ovary syndrome rna binding proteins weighted gene co-expression network analysis. Medicine (General) R5-920 Li M Zeng Z Zhang A Ye Q Su S Xia T WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs |
| description |
Mengxiong Li,1,* Zhi Zeng,2,* Aiqing Zhang,3 Qingjian Ye,4 Shujun Su,4 Tingting Xia5 1Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, People’s Republic of China; 2The Department of Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 5Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tingting Xia Tel +86-020-85256032Email xiatting@mail.sysu.edu.cnObjective: Dysfunction of cumulus granulosa cells has been suggested as a contributor to abnormal folliculogenesis and the development of polycystic ovary syndrome (PCOS), but the underlying molecular mechanisms remain unclear. Recent studies indicate that circular RNAs (circRNAs) exert important roles for diseases. We aimed to screen crucial circRNAs of PCOS patients and predict their functions.Methods: The high-throughput datasets of circRNAs (GSE145296), microRNAs (miRNAs; GSE72274) and messenger RNAs (mRNAs; GSE155489) in cumulus cells of PCOS patients and controls were collected from the Gene Expression Omnibus database. Differentially expressed circRNAs (DECs), miRNAs (DEMs) and protein-coding genes (DEGs) were identified by the limma method. The weighted correlation network analysis (WGCNA) was conducted using the DECs to mine PCOS-associated modules. Hub DECs in modules were defined as both of |gene significance| and |module membership| > 0.8. The downstream effectors of hub DECs were predicted by constructing DEC-DEM-DEG ceRNA and DEC-RNA binding protein (RBP) networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of circRNAs.Results: A total of 3614 DECs, 3544 DEGs and 1469 DEMs were identified between PCOS and controls. WGCNA analysis yielded five PCOS-related modules, of which 190 DECs were hub circRNAs. Seventeen hub DECs, nine DEMs, and 315 DEGs were identified to construct the ceRNA network, while 56 hub DECs and two DEGs (MBNL2, RBPMS) constituted the circRNA-RBP network. Five hub DECs (hsa_circ_0063309, hsa_circ_0054275, hsa_circ_0056196, hsa_circ_0018108 and hsa_circ_0070987) were overlapped between ceRNA and DEC-MBNL2 regulatory networks and thus they may be pivotal for PCOS. Furthermore, hsa_circ_0099109 could interact with the RBP gene RBPMS. Function analyses showed these circRNAs were inflammation-, apoptosis- or steroidogenesis-related.Conclusion: Aberrant expression of six circRNAs that function as RBP regulators or miRNA sponges may be possible mechanisms underlying the pathogenesis of PCOS by affecting apoptosis and steroidogenesis in cumulus cells.Keywords: circular RNAs, competitive endogenous RNAs, polycystic ovary syndrome, RNA-binding proteins, weighted gene co-expression network analysis |
| format |
article |
| author |
Li M Zeng Z Zhang A Ye Q Su S Xia T |
| author_facet |
Li M Zeng Z Zhang A Ye Q Su S Xia T |
| author_sort |
Li M |
| title |
WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs |
| title_short |
WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs |
| title_full |
WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs |
| title_fullStr |
WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs |
| title_full_unstemmed |
WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs |
| title_sort |
wgcna analysis identifies polycystic ovary syndrome-associated circular rnas that interact with rna-binding proteins and sponge mirnas |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/3f4cb9ccbfa54c3ab71541b65560c80b |
| work_keys_str_mv |
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| _version_ |
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