Polycystic Ovary Syndrome: Novel and Hub LncRNAs in the Insulin Resistance-Associated LncRNA-mRNA Network

Overview

Journal Front Genet

Date 2019 Sep 12

PMID 31507635

Citations 18

Authors

Jun Zhao

Jiayu Huang

Xueying Geng

Weiwei Chu

Shang Li

Zi-Jiang Chen

Yanzhi Du

Affiliations

Soon will be listed here.

Abstract

Polycystic ovary syndrome (PCOS) is a common metabolic and reproductive disorder with an increasing risk for type 2 diabetes. Insulin resistance is a common feature of women with PCOS, but the underlying molecular mechanism remains unclear. This study aimed to screen critical long non-coding RNAs (lncRNAs) that might play pivotal roles in insulin resistance, which could provide candidate biomarkers and potential therapeutic targets for PCOS. Gene expression profiles of the skeletal muscle in patients with PCOS accompanied by insulin resistance and healthy patients were obtained from the publicly available Gene Expression Omnibus (GEO) database. A global triple network including RNA-binding protein, mRNA, and lncRNAs was constructed based on the data from starBase. Then, we extracted an insulin resistance-associated lncRNA-mRNA network (IRLMN) by integrating the data from starBase and GEO. We also performed a weighted gene co-expression network analysis (WGCNA) on the differentially expressed genes between the women with and without PCOS, to identify hub lncRNAs. Additionally, the findings of key lncRNAs were examined in an independent GEO dataset. The expression level of in ovarian granulosa cells was increased in patients with PCOS compared with that in control women. Levels were also increased in PCOS patients with higher BMI, hyperinsulinemia, and higher HOMA-IR values. As a result, was identified as a hub lncRNA based on IRLMN and WGCNA and was highly expressed in ovarian granulosa cells, skeletal muscle, and subcutaneous and omental adipose tissues of patients with insulin resistance. This study showed the differences between lncRNA and mRNA profiles from healthy women and women with PCOS and insulin resistance. Here, we demonstrated that RP11-151A6.4 might play a vital role in insulin resistance, androgen excess, and adipose dysfunction in patients with PCOS. Further study concerning RP11-151A6.4 could elucidate the underlying mechanisms of insulin resistance.

Citing Articles

LncRNA XIST Protects Against Polycystic Ovary Syndrome via the Regulation of miR-212-3p/RASA1 Axis.

Xu X, Yin C, Dong B, Li Y, Liu S, Chen J Biochem Genet. 2024; .

PMID: 38609670 DOI: 10.1007/s10528-024-10777-7.

The functional role of lncRNAs as ceRNAs in both ovarian processes and associated diseases.

Usman M, Li A, Wu D, Qinyan Y, Yi L, He G Noncoding RNA Res. 2023; 9(1):165-177.

PMID: 38075201 PMC: 10709095. DOI: 10.1016/j.ncrna.2023.11.008.

KAZN as a diagnostic marker in ovarian cancer: a comprehensive analysis based on microarray, mRNA-sequencing, and methylation data.

Zhu S, Bao H, Zhang M, Liu H, Wang Y, Lin C BMC Cancer. 2022; 22(1):662.

PMID: 35710397 PMC: 9204993. DOI: 10.1186/s12885-022-09747-2.

Novel Hub genes co-expression network mediates dysfunction in a model of polycystic ovary syndrome.

Xi S, Li W, Li Z, Lin W, Chen L, Tian C Am J Transl Res. 2022; 14(3):1979-1990.

PMID: 35422941 PMC: 8991170.

Deconstructing a Syndrome: Genomic Insights Into PCOS Causal Mechanisms and Classification.

Dapas M, Dunaif A Endocr Rev. 2022; 43(6):927-965.

PMID: 35026001 PMC: 9695127. DOI: 10.1210/endrev/bnac001.

References

Dunaif A, Wu X, Lee A, Diamanti-Kandarakis E . Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS). Am J Physiol Endocrinol Metab. 2001; 281(2):E392-9. DOI: 10.1152/ajpendo.2001.281.2.E392. View

Saltiel A, Kahn C . Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001; 414(6865):799-806. DOI: 10.1038/414799a. View

Ek I, Arner P, Ryden M, Holm C, Thorne A, Hoffstedt J . A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes. 2002; 51(2):484-92. DOI: 10.2337/diabetes.51.2.484. View

Zeleznik A, Saxena D, Little-Ihrig L . Protein kinase B is obligatory for follicle-stimulating hormone-induced granulosa cell differentiation. Endocrinology. 2003; 144(9):3985-94. DOI: 10.1210/en.2003-0293. View

. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81(1):19-25. DOI: 10.1016/j.fertnstert.2003.10.004. View

. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004; 363(9403):157-63. DOI: 10.1016/S0140-6736(03)15268-3. View

Zhang B, Horvath S . A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol. 2006; 4:Article17. DOI: 10.2202/1544-6115.1128. View

Draznin B . Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: the two sides of a coin. Diabetes. 2006; 55(8):2392-7. DOI: 10.2337/db06-0391. View

Escobar-Morreale H, San Millan J . Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab. 2007; 18(7):266-72. DOI: 10.1016/j.tem.2007.07.003. View

10.

Hojlund K, Glintborg D, Andersen N, Birk J, Treebak J, Frosig C . Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment. Diabetes. 2007; 57(2):357-66. DOI: 10.2337/db07-0706. View

11.

Roy P, Alevizaki M, Huhtaniemi I . In vitro bioassays for androgens and their diagnostic applications. Hum Reprod Update. 2007; 14(1):73-82. DOI: 10.1093/humupd/dmm038. View

12.

Dumesic D, Abbott D . Implications of polycystic ovary syndrome on oocyte development. Semin Reprod Med. 2008; 26(1):53-61. PMC: 2655636. DOI: 10.1055/s-2007-992925. View

13.

Skov V, Glintborg D, Knudsen S, Tan Q, Jensen T, Kruse T . Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome. PLoS One. 2008; 3(6):e2466. PMC: 2413008. DOI: 10.1371/journal.pone.0002466. View

14.

Nestler J, Powers L, Matt D, Steingold K, Plymate S, Rittmaster R . A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab. 1991; 72(1):83-9. DOI: 10.1210/jcem-72-1-83. View

15.

Langfelder P, Horvath S . WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008; 9:559. PMC: 2631488. DOI: 10.1186/1471-2105-9-559. View

16.

Li C, Li X, Miao Y, Wang Q, Jiang W, Xu C . SubpathwayMiner: a software package for flexible identification of pathways. Nucleic Acids Res. 2009; 37(19):e131. PMC: 2770656. DOI: 10.1093/nar/gkp667. View

17.

Hardy O, Perugini R, Nicoloro S, Gallagher-Dorval K, Puri V, Straubhaar J . Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity. Surg Obes Relat Dis. 2010; 7(1):60-7. PMC: 2980798. DOI: 10.1016/j.soard.2010.05.013. View

18.

Tosi F, Negri C, Brun E, Castello R, Faccini G, Bonora E . Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women. Eur J Endocrinol. 2010; 164(2):197-203. DOI: 10.1530/EJE-10-0782. View

19.

Corkey B . Banting lecture 2011: hyperinsulinemia: cause or consequence?. Diabetes. 2011; 61(1):4-13. PMC: 3237642. DOI: 10.2337/db11-1483. View

20.

Hunzicker-Dunn M, Lopez-Biladeau B, Law N, Fiedler S, Carr D, Maizels E . PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells. Proc Natl Acad Sci U S A. 2012; 109(44):E2979-88. PMC: 3497822. DOI: 10.1073/pnas.1205661109. View