H19 LncRNA Alters Stromal Cell Growth Via IGF Signaling in the Endometrium of Women with Endometriosis

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2015 Jun 20

PMID 26089099

Citations 98

Authors

Sanaz Ghazal

Brett McKinnon

Jichun Zhou

Martin Mueller

Yi Men

Lihua Yang

Michael Mueller

Clare Flannery

Yingqun Huang

Hugh S Taylor

Affiliations

Soon will be listed here.

Abstract

Endometriosis affects approximately 15% of reproductive aged women and is associated with chronic pelvic pain and infertility. However, the molecular mechanisms by which endometriosis impacts fertility are poorly understood. The developmentally regulated, imprinted H19 long noncoding RNA (lncRNA) functions to reduce the bioavailability of microRNA let-7 by acting as a molecular sponge. Here we report that H19 expression is significantly decreased in the eutopic endometrium of women with endometriosis as compared to normal controls. We show that decreased H19 increases let-7 activity, which in turn inhibits Igf1r expression at the post-transcriptional level, thereby contributing to reduced proliferation of endometrial stromal cells. We propose that perturbation of this newly identified H19/Let-7/IGF1R regulatory pathway may contribute to impaired endometrial preparation and receptivity for pregnancy in women with endometriosis. Our finding represents the first example of a lncRNA-based mechanism in endometriosis and its associated infertility, thus holding potential in the development of novel therapeutics for women with endometriosis and infertility.

Citing Articles

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References

Macer M, Taylor H . Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012; 39(4):535-49. PMC: 3538128. DOI: 10.1016/j.ogc.2012.10.002. View

Dey B, Pfeifer K, Dutta A . The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration. Genes Dev. 2014; 28(5):491-501. PMC: 3950346. DOI: 10.1101/gad.234419.113. View

Kallen A, Zhou X, Xu J, Qiao C, Ma J, Yan L . The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell. 2013; 52(1):101-12. PMC: 3843377. DOI: 10.1016/j.molcel.2013.08.027. View

Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L, Smits G . The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat Cell Biol. 2012; 14(7):659-65. PMC: 3389517. DOI: 10.1038/ncb2521. View

Fabian M, Sonenberg N . The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol. 2012; 19(6):586-93. DOI: 10.1038/nsmb.2296. View

Yang H, Zhou Y, Edelshain B, Schatz F, Lockwood C, Taylor H . FKBP4 is regulated by HOXA10 during decidualization and in endometriosis. Reproduction. 2012; 143(4):531-8. DOI: 10.1530/REP-11-0438. View

Zhu H, Shyh-Chang N, V Segre A, Shinoda G, Shah S, Einhorn W . The Lin28/let-7 axis regulates glucose metabolism. Cell. 2011; 147(1):81-94. PMC: 3353524. DOI: 10.1016/j.cell.2011.08.033. View

Gabory A, Jammes H, Dandolo L . The H19 locus: role of an imprinted non-coding RNA in growth and development. Bioessays. 2010; 32(6):473-80. DOI: 10.1002/bies.200900170. View

Korucuoglu U, Biri A, Konac E, Alp E, Onen I, Ilhan M . Expression of the imprinted IGF2 and H19 genes in the endometrium of cases with unexplained infertility. Eur J Obstet Gynecol Reprod Biol. 2010; 149(1):77-81. DOI: 10.1016/j.ejogrb.2009.12.007. View

10.

Meuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, DHooghe T . High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril. 2008; 92(1):68-74. DOI: 10.1016/j.fertnstert.2008.04.056. View

11.

Ruijter J, Ramakers C, Hoogaars W, Karlen Y, Bakker O, van den Hoff M . Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res. 2009; 37(6):e45. PMC: 2665230. DOI: 10.1093/nar/gkp045. View

12.

Bromer J, Aldad T, Taylor H . Defining the proliferative phase endometrial defect. Fertil Steril. 2008; 91(3):698-704. PMC: 2699408. DOI: 10.1016/j.fertnstert.2007.12.066. View

13.

Roush S, Slack F . The let-7 family of microRNAs. Trends Cell Biol. 2008; 18(10):505-16. DOI: 10.1016/j.tcb.2008.07.007. View

14.

Moldovan G, Pfander B, Jentsch S . PCNA, the maestro of the replication fork. Cell. 2007; 129(4):665-79. DOI: 10.1016/j.cell.2007.05.003. View

15.

Ivanga M, Labrie Y, Calvo E, Belleau P, Martel C, Luu-The V . Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus. Physiol Genomics. 2007; 29(1):13-23. DOI: 10.1152/physiolgenomics.00291.2005. View

16.

McCampbell A, Broaddus R, Loose D, Davies P . Overexpression of the insulin-like growth factor I receptor and activation of the AKT pathway in hyperplastic endometrium. Clin Cancer Res. 2006; 12(21):6373-8. DOI: 10.1158/1078-0432.CCR-06-0912. View

17.

Yan L, Zhou J, Gao Y, Ghazal S, Lu L, Bellone S . Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene. 2014; 34(23):3076-84. DOI: 10.1038/onc.2014.236. View

18.

Zhu Y, Song X, Wang J, Li Y, Yang Y, Yang T . Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition. Expert Opin Biol Ther. 2014; 15(2):163-80. DOI: 10.1517/14712598.2015.960837. View

19.

Gao Y, Wu F, Zhou J, Yan L, Jurczak M, Lee H . The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Res. 2014; 42(22):13799-811. PMC: 4267628. DOI: 10.1093/nar/gku1160. View

20.

Hurst B, Shimp K, Elliot M, Marshburn P, Parsons J, Bahrani-Mostafavi Z . Molecular evaluation of proliferative-phase endometrium may provide insight about the underlying causes of infertility in women with endometriosis. Arch Gynecol Obstet. 2013; 289(5):1119-24. DOI: 10.1007/s00404-013-3103-6. View