Novel Hub Genes Co-expression Network Mediates Dysfunction in a Model of Polycystic Ovary Syndrome

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2022 Apr 15

PMID 35422941

Authors

Sujuan Xi

Weihao Li

Zaiyi Li

Wenjing Lin

Lin Chen

Chengzi Tian

Yazhu Yang

Lin Ma

Affiliations

Soon will be listed here.

Abstract

Background: This study aimed to integrate DNA methylation, miRNA, and mRNA microarray data to construct a gene co-expression network for polycystic ovarian syndrome (PCOS).

Methods: The weighted gene co-expression network analysis (WGCNA) was conducted to construct a PCOS-related co-expression network by using the GEO public datasets. We performed Gene Ontology and KEGG pathway enrichment analyses for a further exploration of gene function in networks. Finally, the dysfunction module consisting of a co-expression network was mapped to the PCOS patients and tried to provide guidance to the PCOS phenotyping.

Results: Three modules (Midnightbule, Pink, and Red) were identified to be PCOS-related by WGCNA analysis. These module-related genes were enriched in cell response to stimulus, PI3K-Akt signaling pathway, insulin biological process, signaling pathway, and cytokine-cytokine receptor interaction biological processes. The multiple-factor network, including miRNA-lncRNA and DNA methylation-mRNA interaction, was closely associated with PCOS dysfunction.

Conclusion: Our study render a novel insight into the mechanisms and might provide candidate biomarkers and therapeutic targets for the classification of PCOS dysfunction.

Citing Articles

Whispers of the polycystic ovary syndrome theater: Directing role of long noncoding RNAs.

Lin X, Nie X, Deng P, Wang L, Hu C, Jin N Noncoding RNA Res. 2024; 9(4):1023-1032.

PMID: 39022674 PMC: 11254504. DOI: 10.1016/j.ncrna.2024.05.003.

Unveiling Key Biomarkers and Therapeutic Drugs in Polycystic Ovary Syndrome (PCOS) Through Pathway Enrichment Analysis and Hub Gene-miRNA Networks.

Heidarzadehpilehrood R, Pirhoushiaran M, Osman M, Ling K, Hamid H Iran J Pharm Res. 2024; 22(1):e139985.

PMID: 38444712 PMC: 10912876. DOI: 10.5812/ijpr-139985.

Identification and immune features of cuproptosis-related molecular clusters in polycystic ovary syndrome.

Su Z, Su W, Li C, Ding P, Wang Y Sci Rep. 2023; 13(1):980.

PMID: 36653385 PMC: 9849323. DOI: 10.1038/s41598-022-27326-0.

References

Hou Y, Wang Y, Xu S, Qi G, Wu X . Bioinformatics identification of microRNAs involved in polycystic ovary syndrome based on microarray data. Mol Med Rep. 2019; 20(1):281-291. PMC: 6579986. DOI: 10.3892/mmr.2019.10253. View

Escobar-Morreale H . Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018; 14(5):270-284. DOI: 10.1038/nrendo.2018.24. View

Wang W, Ji J, Li J, Ren Q, Gu J, Zhao Y . Several critical genes and microRNAs associated with the development of polycystic ovary syndrome. Ann Endocrinol (Paris). 2020; 81(1):18-27. DOI: 10.1016/j.ando.2019.10.002. View

Wang Y, Xu S, Wang Y, Qi G, Hou Y, Sun C . Identification and potential value of candidate microRNAs in granulosa cells of polycystic ovary syndrome. Technol Health Care. 2019; 27(6):579-587. DOI: 10.3233/THC-181510. View

Day F, Hinds D, Tung J, Stolk L, Styrkarsdottir U, Saxena R . Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat Commun. 2015; 6:8464. PMC: 4598835. DOI: 10.1038/ncomms9464. View

Hayes M, Urbanek M, Ehrmann D, Armstrong L, Lee J, Sisk R . Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nat Commun. 2015; 6:7502. PMC: 4557132. DOI: 10.1038/ncomms8502. View

Alvarez-Blasco F, Botella-Carretero J, San Millan J, Escobar-Morreale H . Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med. 2006; 166(19):2081-6. DOI: 10.1001/archinte.166.19.2081. View

Qi X, Yun C, Sun L, Xia J, Wu Q, Wang Y . Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat Med. 2019; 25(8):1225-1233. PMC: 7376369. DOI: 10.1038/s41591-019-0509-0. View

Chen Z, Zhao H, He L, Shi Y, Qin Y, Shi Y . Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet. 2010; 43(1):55-9. DOI: 10.1038/ng.732. View

10.

Norman R, Dewailly D, Legro R, Hickey T . Polycystic ovary syndrome. Lancet. 2007; 370(9588):685-97. DOI: 10.1016/S0140-6736(07)61345-2. View

11.

Kakoly N, Khomami M, Joham A, Cooray S, Misso M, Norman R . Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression. Hum Reprod Update. 2018; 24(4):455-467. DOI: 10.1093/humupd/dmy007. View

12.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

13.

Dokras A, Stener-Victorin E, Yildiz B, Li R, Ottey S, Shah D . Androgen Excess- Polycystic Ovary Syndrome Society: position statement on depression, anxiety, quality of life, and eating disorders in polycystic ovary syndrome. Fertil Steril. 2018; 109(5):888-899. DOI: 10.1016/j.fertnstert.2018.01.038. View

14.

Chen B, Xu P, Wang J, Zhang C . The role of MiRNA in polycystic ovary syndrome (PCOS). Gene. 2019; 706:91-96. DOI: 10.1016/j.gene.2019.04.082. View

15.

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

16.

Zeng Z, Lin X, Xia T, Liu W, Tian X, Li M . Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis. Biomed Res Int. 2020; 2020:1817094. PMC: 7666708. DOI: 10.1155/2020/1817094. View

17.

Risal S, Pei Y, Lu H, Manti M, Fornes R, Pui H . Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nat Med. 2019; 25(12):1894-1904. DOI: 10.1038/s41591-019-0666-1. View

18.

Xia H, Zhao Y . miR-155 is high-expressed in polycystic ovarian syndrome and promotes cell proliferation and migration through targeting PDCD4 in KGN cells. Artif Cells Nanomed Biotechnol. 2019; 48(1):197-205. DOI: 10.1080/21691401.2019.1699826. View

19.

Huang J, Zhao J, Geng X, Chu W, Li S, Chen Z . Long non-coding RNA lnc-CCNL1-3:1 promotes granulosa cell apoptosis and suppresses glucose uptake in women with polycystic ovary syndrome. Mol Ther Nucleic Acids. 2021; 23:614-628. PMC: 7819816. DOI: 10.1016/j.omtn.2020.12.008. View

20.

Jiao J, Shi B, Wang T, Fang Y, Cao T, Zhou Y . 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. DOI: 10.1093/humrep/dey255. View