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Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome

  • Authors:
    • Li Liu
    • Dongyun He
    • Yang Wang
    • Minjia Sheng
  • View Affiliations / Copyright

    Affiliations: Reproductive Medical Center, Department of Gynecology and Obstetrics, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China, Department of Dermatology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin 130031, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2138-2150
    |
    Published online on: February 26, 2020
       https://doi.org/10.3892/mmr.2020.11005
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Abstract

The present study aimed to identify potentially important biomarkers associated with polycystic ovary syndrome (PCOS) by integrating DNA methylation with transcriptome profiling. The transcription (E‑MTAB‑3768) and methylation (E‑MTAB‑3777) datasets were retrieved from ArrayExpress. Paired transcription and methylation profiling data of 10 cases of PCOS and 10 healthy controls were available for screening differentially expressed genes (DEGs) and differentially methylated genes (DMGs). Genes with a negative correlation between expression levels and methylation levels were retained by correlation analysis to construct a protein‑protein interaction (PPI) network. Subsequently, functional and pathway enrichment analyses were performed to identify genes in the PPI network. Additionally, a disease‑associated pathway network was also established. A total of 491 overlapping genes, and the expression levels of 237 genes, were negatively correlated with their methylation levels. Functional enrichment analysis revealed that genes in the PPI network were mainly involved with biological processes of cellular response to stress, negative regulation of the biosynthetic process, and regulation of cell proliferation. The constructed pathway network associated with PCOS led to the identification of four important genes (SPP1, F2R, IL12B and RBP4) and two important pathways (Jak‑STAT signaling pathway and neuroactive ligand‑receptor interaction). Taken, together, the results from the present study have revealed numerous important genes with abnormal DNA methylation levels and altered mRNA expression levels, along with their associated functions and pathways. These findings may contribute to an improved understanding of the possible pathophysiology of PCOS.
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1 

Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, Lizneva D, Natterson-Horowtiz B, Teede HJ and Yildiz BO: Polycystic ovary syndrome. Nat Rev Dis Primers. 2:160582016. View Article : Google Scholar : PubMed/NCBI

2 

Neven ACH, Laven J, Teede HJ and Boyle JA: A summary on polycystic ovary syndrome: Diagnostic criteria, prevalence, clinical manifestations, and management according to the latest international guidelines. Semin Reprod Med. 36:5–12. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Strauss JF, Modi BP and McAllister JM: The genetics of polycystic ovary syndrome: From genome-wide association to molecular mechanisms. Reproductive Medicine for Clinical Practice. Springer; pp. 25–33. 2018, View Article : Google Scholar

4 

Zhong Z, Li F, Li Y, Qin S, Wen C, Fu Y and Xiao Q: Inhibition of microRNA-19b promotes ovarian granulosa cell proliferation by targeting IGF-1 in polycystic ovary syndrome. Mol Med Rep. 17:4889–4898. 2018.PubMed/NCBI

5 

Barber T and Franks S: Genetic and environmental factors in the etiology of polycystic ovary syndrome. The Ovary. Elsevier; pp. 437–459. 2019, View Article : Google Scholar

6 

Guo F, Li X, Liang D, Li T, Zhu P, Guo H, Wu X, Wen L, Gu TP, Hu B, et al: Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell. 15:447–459. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Wijaya AD, Febri RR, Hestiantoro A and Asmarinah: DNA methylation analysis of anti-mullerian hormone gene in ovarian granulosa cells in PCOS patients. J Phys Conf Ser. 1073:0320772018. View Article : Google Scholar

8 

Xu N, Azziz R and Goodarzi MO: Epigenetics in polycystic ovary syndrome: A pilot study of global DNA methylation. Fertil Steril. 94:781–783.e1. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Shen HR, Qiu LH, Zhang ZQ, Qin YY, Cao C and Di W: Genome-wide methylated DNA immunoprecipitation analysis of patients with polycystic ovary syndrome. PLoS One. 8:e648012013. View Article : Google Scholar : PubMed/NCBI

10 

Xu J, Xiao B, Peng Z, Wang L, Du L, Niu W and Sun Y: Comprehensive analysis of genome-wide DNA methylation across human polycystic ovary syndrome ovary granulosa cell. Oncotarget. 7:27899–27909. 2016.PubMed/NCBI

11 

Wang XX, Wei JZ, Jiao J, Jiang SY, Yu DH and Li D: Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development. Oncotarget. 5:6603–6610. 2014.PubMed/NCBI

12 

Parkinson H, Sarkans U, Kolesnikov N, Abeygunawardena N, Burdett T, Dylag M, Emam I, Farne A, Hastings E, Holloway E, et al: ArrayExpress update-an archive of microarray and high-throughput sequencing-based functional genomics experiments. Nucleic Acids Res. 39:D1002–D1004. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W and Smyth GK: Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43:e472015. View Article : Google Scholar : PubMed/NCBI

14 

Rao Y, Lee Y, Jarjoura D, Ruppert AS, Liu CG, Hsu JC and Hagan JP: A comparison of normalization techniques for microRNA microarray data. Stat Appl Genet Mol Biol. 7:Article222008. View Article : Google Scholar : PubMed/NCBI

15 

Smyth GK: Limma: Linear models for microarray data. Bioinformatics and computational biology solutions using R and Bioconductor. Springer; pp. 397–420. 2005, View Article : Google Scholar

16 

Benjamini Y and Hochberg Y: Controlling the false discovery rate: A practical and powerful approach to multiple testing. J Royal Stat Soc Series B. 57:289–300. 1995.

17 

Uchino H, Ito M, Kazumata K, Hama Y, Hamauchi S, Terasaka S, Sasaki H and Houkin K: Circulating miRNome profiling in moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line. BMC Med Genomics. 11:722018. View Article : Google Scholar : PubMed/NCBI

18 

Wang L, Cao C, Ma Q, Zeng Q, Wang H, Cheng Z, Zhu G, Qi J, Ma H, Nian H and Wang Y: RNA-seq analyses of multiple meristems of soybean: Novel and alternative transcripts, evolutionary and functional implications. BMC Plant Biol. 14:1692014. View Article : Google Scholar : PubMed/NCBI

19 

Deza MM and Deza E: Encyclopedia of Distances. Encyclopedia of Distances. Springer; Berlin, Heidelberg: 2009, View Article : Google Scholar

20 

Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, et al: The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45:D362–D368. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Davis AP, Murphy CG, Johnson R, Lay JM, Lennon-Hopkins K, Saraceni-Richards C, Sciaky D, King BL, Rosenstein MC, Wiegers TC and Mattingly CJ: The comparative toxicogenomics database: Update 2013. Nucleic Acids Res. 41:D1104–D1114. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Azziz R: PCOS in 2015: New insights into the genetics of polycystic ovary syndrome. Nat Rev Endocrinol. 12:74–75. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Margetic S, Gazzola C, Pegg GG and Hill RA: Leptin: A review of its peripheral actions and interactions. Int J Obes Relat Metab Disord. 26:1407–1433. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Nomair AM, Aref NK, Rizwan F, Ezzo OH and Hassan N: Serum leptin level in obese women with polycystic ovary syndrome and its relation to insulin resistance. Asian Pac J Reproduction. 3:288–294. 2014. View Article : Google Scholar

28 

Marciniak A and Starczewski A: The role of leptin in polycystic ovary syndrome. Pol Merkur Lekarski. 25:390–393. 2008.(In Polish). PubMed/NCBI

29 

Zheng SH, Du DF and Li XL: Leptin levels in women with polycystic ovary syndrome: A systematic review and a meta-analysis. Reprod Sci. 24:656–670. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Flier JS: Leptin expression and action: New experimental paradigms. Proc Natl Acad Sci USA. 94:4242–4245. 1997. View Article : Google Scholar : PubMed/NCBI

31 

Ghilardi N and Skoda RC: The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. Mol Endocrinol. 11:393–399. 1997. View Article : Google Scholar : PubMed/NCBI

32 

Kloek C, Haq AK, Dunn SL, Lavery HJ, Banks AS and Myers MG Jr: Regulation of Jak kinases by intracellular leptin receptor sequences. J Biol Chem. 277:41547–41555. 2002. View Article : Google Scholar : PubMed/NCBI

33 

Maliqueo M, Sundström Poromaa I, Vanky E, Fornes R, Benrick A, Åkerud H, Stridsklev S, Labrie F, Jansson T and Stener-Victorin E: Placental STAT3 signaling is activated in women with polycystic ovary syndrome. Hum Reprod. 30:692–700. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Chen MJ, Yang WS, Chen CL, Wu MY, Yang YS and Ho HN: The relationship between anti-Müllerian hormone, androgen and insulin resistance on the number of antral follicles in women with polycystic ovary syndrome. Hum Reprod. 23:952–957. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Maliqueo M, Clementi M, Gabler F, Johnson MC, Palomino A, Sir-Petermann T and Vega M: Expression of steroid receptors and proteins related to apoptosis in endometria of women with polycystic ovary syndrome. Fertil Steril. 80 (Suppl 2):S812–S819. 2003. View Article : Google Scholar

36 

Du Y, Wang J, Lyu B, Yan G and Sun H: Impaired granulosa cells promote self-damage by regulating the generation of macrophage in polycystic ovary syndrome. Int J Clin Exp Pathol. 9:10992–11002. 2016.

37 

Das M, Djahanbakhch O, Hacihanefioglu B, Saridogan E, Ikram M, Ghali L, Raveendran M and Storey A: Granulosa cell survival and proliferation are altered in polycystic ovary syndrome. J Clin Endocrinol Metab. 93:881–887. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Fu X, He Y, Wang X, Peng D, Chen X, Li X and Wan Q: MicroRNA-16 promotes ovarian granulosa cell proliferation and suppresses apoptosis through targeting PDCD4 in polycystic ovarian syndrome. Cell Physiol Biochem. 48:670–682. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu L, He D, Wang Y and Sheng M: Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome. Mol Med Rep 21: 2138-2150, 2020.
APA
Liu, L., He, D., Wang, Y., & Sheng, M. (2020). Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome. Molecular Medicine Reports, 21, 2138-2150. https://doi.org/10.3892/mmr.2020.11005
MLA
Liu, L., He, D., Wang, Y., Sheng, M."Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome". Molecular Medicine Reports 21.5 (2020): 2138-2150.
Chicago
Liu, L., He, D., Wang, Y., Sheng, M."Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome". Molecular Medicine Reports 21, no. 5 (2020): 2138-2150. https://doi.org/10.3892/mmr.2020.11005
Copy and paste a formatted citation
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Spandidos Publications style
Liu L, He D, Wang Y and Sheng M: Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome. Mol Med Rep 21: 2138-2150, 2020.
APA
Liu, L., He, D., Wang, Y., & Sheng, M. (2020). Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome. Molecular Medicine Reports, 21, 2138-2150. https://doi.org/10.3892/mmr.2020.11005
MLA
Liu, L., He, D., Wang, Y., Sheng, M."Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome". Molecular Medicine Reports 21.5 (2020): 2138-2150.
Chicago
Liu, L., He, D., Wang, Y., Sheng, M."Integrated analysis of DNA methylation and transcriptome profiling of polycystic ovary syndrome". Molecular Medicine Reports 21, no. 5 (2020): 2138-2150. https://doi.org/10.3892/mmr.2020.11005
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