Bioinformatics analysis of circular RNAs differential expression in polycystic ovary syndrome_West China Medical Journal

Authors：

WU Denghui ¹ , YU Jinlan ² , ZHANG Jiao ³ , YANG Lizhen ⁴ , SUN Yuhua ⁴ ,  ZHANG Yuehui ⁴

1. The First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P. R. China;
2. Department of Gynecology, Daoli District People’s Hospital, Harbin, Heilongjiang 150040, P. R. China;
3. Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P. R. China;
4. Department of Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P. R. China;

Corresponding author：

ZHANG Yuehui, Email: chizishui-04@163.com

Keywords：

Polycystic ovary syndrome; bioinformatics; circular RNA; microRNA

DOI：

10.7507/1002-0179.202012054

Video：

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Objective To explore the differential expression of circular RNAs (circRNAs) in polycystic ovary syndrome (PCOS) by bioinformatics, and predict the microRNAs (miRNAs) associated with them. Methods The expression profile of cumulus cells gene chip in PCOS was searched in the Gene Expression Omnibus database, and differential circRNAs were screened by GEO2R tool of the database. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathways of different circRNA genes were analyzed using the DAVID 6.8 database. Circular RNA interactome was used to predict the potential regulated miRNAs. Cytoscape software was used to establish circRNA-miRNA network map. The potential regulatory miRNAs were predicted by the 10 circRNAs with the most significant differences in up-regulation and down-regulation. Results A total of 247 circRNAs were obtained in PCOS, and 277 miRNAs binding to up-regulated circRNA genes and 125 miRNAs binding to down-regulated circRNA genes were predicted. The top 10 miRNAs that could bind to multiple differential circRNAs were hsa-miR-557, hsa-miR-507, hsa-miR-224, hsa-miR-136, hsa-miR-127-5p, hsa-miR-579, hsa-miR-502-5p, hsa-miR-186, hsa-miR-1253, and hsa-miR-432. Conclusion The differential expression analysis of circRNAs is helpful to understand the main role of circRNAs in PCOS, and the prediction of potential regulated miRNAs can help to understand the pathogenesis of the disease.

Citation： WU Denghui, YU Jinlan, ZHANG Jiao, YANG Lizhen, SUN Yuhua, ZHANG Yuehui. Bioinformatics analysis of circular RNAs differential expression in polycystic ovary syndrome. West China Medical Journal, 2022, 37(2): 231-236. doi: 10.7507/1002-0179.202012054 Copy

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2.	Meier RK. Polycystic ovary syndrome. Nurs Clin North Am, 2018, 53(3): 407-420.
3.	Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol, 2018, 14(5): 270-284.
4.	齐玉涵, 刘泽鹏, 张伟杰, 等. 环状 RNA 研究进展. 生理学报, 2019, 71(4): 613-624.
5.	Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol, 2015, 12(4): 381-388.
6.	高嘉良, 陈光, 何浩强, 等. 环状 RNA: 人类疾病研究的新领域. 中国中药杂志, 2018, 43(3): 457-462.
7.	Qian L, Yu S, Chen Z, et al. The emerging role of circRNAs and their clinical significance in human cancers. Biochim Biophys Acta Rev Cancer, 2018, 1870(2): 247-260.
8.	Deng L, Chen Q, Xie J, et al. circPUM1 promotes polycystic ovary syndrome progression by sponging to miR-760. Gene, 2020, 754: 144903.
9.	Cooper DA, Cortés-López M, Miura P. Genome-wide circRNA profiling from RNA-seq data. Methods Mol Biol, 2018, 1724: 27-41.
10.	Sanger HL, Klotz G, Riesner D, et al. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci USA, 1976, 73(11): 3852-3856.
11.	Aghaee-Bakhtiari SH. Online databases and circular RNAs. Adv Exp Med Biol, 2018, 1087: 35-38.
12.	Li Y, Chen C, Ma Y, et al. Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS). Life Sci, 2019, 228: 167-175.
13.	Jiao J, Shi B, Wang T, et al. Characterization of long non-coding RNA and messenger RNA profiles in follicular fluid from mature and immature ovarian follicles of healthy women and women with polycystic ovary syndrome. Hum Reprod, 2018, 33(9): 1735-1748.
14.	Li Y, Zhang J, Liu YD, et al. Long non-coding RNA TUG1 and its molecular mechanisms in polycystic ovary syndrome. RNA Biol, 2020, 17(12): 1798-1810.
15.	Wang W, Ji J, Li J, et al. Several critical genes and microRNAs associated with the development of polycystic ovary syndrome. Ann Endocrinol (Paris), 2020, 81(1): 18-27.
16.	Liu J, Ding J, Qu B, et al. CircPSMC3 alleviates the symptoms of PCOS by sponging miR-296-3p and regulating PTEN expression. J Cell Mol Med, 2020, 24(18): 11001-11011.
17.	Wang LP, Peng XY, Lv XQ, et al. High throughput circRNAs sequencing profile of follicle fluid exosomes of polycystic ovary syndrome patients. J Cell Physiol, 2019, 234(9): 15537-15547.
18.	Palomba S, Daolio J, La Sala GB. Oocyte competence in women with polycystic ovary syndrome. Trends Endocrinol Metab, 2017, 28(3): 186-198.
19.	Kung CP, Leu JI, Basu S, et al. The P72R polymorphism of p53 predisposes to obesity and metabolic dysfunction. Cell Rep, 2016, 14(10): 2413-2425.
20.	Brunet A. Aging and the control of the insulin-FOXO signaling pathway. Med Sci (Paris), 2012, 28(3): 316-320.
21.	Sen R, Ghosal S, Das S, et al. Competing endogenous RNA: the key to posttranscriptional regulation. Sci World J, 2014, 2014: 896206.
22.	Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 2013, 495(7441): 333-338.
23.	Jia C, Wang S, Yin C, et al. Loss of hsa_circ_0118530 inhibits human granulosa-like tumor cell line KGN cell injury by sponging miR-136. Gene, 2020, 744: 144591.
24.	Ma Z, Zhao H, Zhang Y, et al. Novel circular RNA expression in the cumulus cells of patients with polycystic ovary syndrome. Arch Gynecol Obstet, 2019, 299(6): 1715-1725.
25.	Song Y, Yu G, Xiang Y, et al. Altered miR-186 and miR-135a contribute to granulosa cell dysfunction by targeting ESR2: a possible role in polycystic ovary syndrome. Mol Cell Endocrinol, 2019, 494: 110478.
26.	Tang FH, Chang W, Tsai EM, et al. Investigating novel genes potentially involved in endometrial adenocarcinoma using next-generation sequencing and bioinformatic approaches. Int J Med Sci, 2019, 16(10): 1338-1348.
27.	Ying H, Lyu J, Ying T, et al. Risk miRNA screening of ovarian cancer based on miRNA functional synergistic network. J Ovarian Res, 2014, 7: 9.

1. Lizneva D, Suturina L, Walker W, et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril, 2016, 106(1): 6-15.
2. Meier RK. Polycystic ovary syndrome. Nurs Clin North Am, 2018, 53(3): 407-420.
3. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol, 2018, 14(5): 270-284.
4. 齐玉涵, 刘泽鹏, 张伟杰, 等. 环状 RNA 研究进展. 生理学报, 2019, 71(4): 613-624.
5. Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol, 2015, 12(4): 381-388.
6. 高嘉良, 陈光, 何浩强, 等. 环状 RNA: 人类疾病研究的新领域. 中国中药杂志, 2018, 43(3): 457-462.
7. Qian L, Yu S, Chen Z, et al. The emerging role of circRNAs and their clinical significance in human cancers. Biochim Biophys Acta Rev Cancer, 2018, 1870(2): 247-260.
8. Deng L, Chen Q, Xie J, et al. circPUM1 promotes polycystic ovary syndrome progression by sponging to miR-760. Gene, 2020, 754: 144903.
9. Cooper DA, Cortés-López M, Miura P. Genome-wide circRNA profiling from RNA-seq data. Methods Mol Biol, 2018, 1724: 27-41.
10. Sanger HL, Klotz G, Riesner D, et al. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci USA, 1976, 73(11): 3852-3856.
11. Aghaee-Bakhtiari SH. Online databases and circular RNAs. Adv Exp Med Biol, 2018, 1087: 35-38.
12. Li Y, Chen C, Ma Y, et al. Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS). Life Sci, 2019, 228: 167-175.
13. Jiao J, Shi B, Wang T, et al. Characterization of long non-coding RNA and messenger RNA profiles in follicular fluid from mature and immature ovarian follicles of healthy women and women with polycystic ovary syndrome. Hum Reprod, 2018, 33(9): 1735-1748.
14. Li Y, Zhang J, Liu YD, et al. Long non-coding RNA TUG1 and its molecular mechanisms in polycystic ovary syndrome. RNA Biol, 2020, 17(12): 1798-1810.
15. Wang W, Ji J, Li J, et al. Several critical genes and microRNAs associated with the development of polycystic ovary syndrome. Ann Endocrinol (Paris), 2020, 81(1): 18-27.
16. Liu J, Ding J, Qu B, et al. CircPSMC3 alleviates the symptoms of PCOS by sponging miR-296-3p and regulating PTEN expression. J Cell Mol Med, 2020, 24(18): 11001-11011.
17. Wang LP, Peng XY, Lv XQ, et al. High throughput circRNAs sequencing profile of follicle fluid exosomes of polycystic ovary syndrome patients. J Cell Physiol, 2019, 234(9): 15537-15547.
18. Palomba S, Daolio J, La Sala GB. Oocyte competence in women with polycystic ovary syndrome. Trends Endocrinol Metab, 2017, 28(3): 186-198.
19. Kung CP, Leu JI, Basu S, et al. The P72R polymorphism of p53 predisposes to obesity and metabolic dysfunction. Cell Rep, 2016, 14(10): 2413-2425.
20. Brunet A. Aging and the control of the insulin-FOXO signaling pathway. Med Sci (Paris), 2012, 28(3): 316-320.
21. Sen R, Ghosal S, Das S, et al. Competing endogenous RNA: the key to posttranscriptional regulation. Sci World J, 2014, 2014: 896206.
22. Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 2013, 495(7441): 333-338.
23. Jia C, Wang S, Yin C, et al. Loss of hsa_circ_0118530 inhibits human granulosa-like tumor cell line KGN cell injury by sponging miR-136. Gene, 2020, 744: 144591.
24. Ma Z, Zhao H, Zhang Y, et al. Novel circular RNA expression in the cumulus cells of patients with polycystic ovary syndrome. Arch Gynecol Obstet, 2019, 299(6): 1715-1725.
25. Song Y, Yu G, Xiang Y, et al. Altered miR-186 and miR-135a contribute to granulosa cell dysfunction by targeting ESR2: a possible role in polycystic ovary syndrome. Mol Cell Endocrinol, 2019, 494: 110478.
26. Tang FH, Chang W, Tsai EM, et al. Investigating novel genes potentially involved in endometrial adenocarcinoma using next-generation sequencing and bioinformatic approaches. Int J Med Sci, 2019, 16(10): 1338-1348.
27. Ying H, Lyu J, Ying T, et al. Risk miRNA screening of ovarian cancer based on miRNA functional synergistic network. J Ovarian Res, 2014, 7: 9.

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Bioinformatics analysis of circular RNAs differential expression in polycystic ovary syndrome

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