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Profiles for long non-coding RNAs in ovarian granulosa cells from women with PCOS with or without hyperandrogenism

  • Author Footnotes
    † Contributed equally to this paper
    Li Jin
    Correspondence
    Corresponding Authors.
    Footnotes
    † Contributed equally to this paper
    Affiliations
    International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China
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  • Author Footnotes
    † Contributed equally to this paper
    Qian Yang
    Footnotes
    † Contributed equally to this paper
    Affiliations
    International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China

    Karolinska Institutet Stockholm, Sweden
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  • Chengliang Zhou
    Affiliations
    Woman’s Hospital, School of Medicine, Zhejiang University Zhejiang, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China
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  • Lanxin Liu
    Affiliations
    International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China
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  • Huihui Wang
    Affiliations
    International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China
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  • Min Hou
    Affiliations
    International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China
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  • Yimei Wu
    Affiliations
    International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China
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  • Fengtao Shi
    Affiliations
    International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China
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  • Jianzhong Sheng
    Affiliations
    Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University Zhejiang, China
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  • Hefeng Huang
    Correspondence
    Corresponding Authors.
    Affiliations
    International, Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Huashan Rd. 1961 Shanghai 200030, China

    Woman’s Hospital, School of Medicine, Zhejiang University Zhejiang, China

    Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University Shanghai, China

    Karolinska Institutet Stockholm, Sweden
    Search for articles by this author
  • Author Footnotes
    † Contributed equally to this paper
Published:August 29, 2018DOI:https://doi.org/10.1016/j.rbmo.2018.08.005

      Highlights

      • PCOS patients with hyperandrogenism displayed 3000 and 1030 differentially expressed lncRNAs as compared to Control and PCOS patients without hyperandrogenism.
      • CRHBP remains consistently the up-regulated lncRNA in PCOS with hyperandrogenism whether compared to PCOS without hyperandrogenism or Control patients.
      • Co-expression analysis suggests differentially expressed lncRNAs in PCOS patients with hyperandrogenism probably play their regulatory role by interacting with transcription factor including YY1 and SIX5.
      • GO and Pathway analysis indicated that differential lncRNAs probably cause mitochondrial changes in PCOS with hyperandrogenism.

      Abstract

      Research question

      What is the expression pattern of long non-coding RNAs (lncRNA) in ovarian granulosa cells of women with polycystic ovary syndrome (PCOS) with or without hyperandrogenism?

      Design

      Microarray screening of lncRNA was conducted in ovarian granulosa cells collected from women with PCOS with hyperandrogenism (PCOS-T) or without hyperandrogenism (PCOS-N) and control participants, with four samples in each group. This was followed by hierarchy clustering, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Several candidate lncRNA were randomly selected for quantitative polymerase chain reaction validation in another 54 patients. To predict the regulatory effect of lncRNA on hyperandrogenism, a co-expression network was plotted using differentially hexpressed lncRNA with statistical significance (≥ twofold; P < 0.05) in PCOS-T compared with PCOS-N.

      Results

      A total of 3000 and 1030 differentially expressed lncRNA (≥ twofold change) were detected in PCOS-T compared with control and PCOS-N, respectively. A total of 1361 differentially expressed lncRNA were detected in PCOS-N compared with controls. Corticotropin releasing hormone binding protein is consistently the up-regulated lncRNA with the highest fold-change in PCOS-T compared with either control or PCOS-N. Gene ontology and pathway analysis showed that dysregulated lncRNA in PCOS-T have a regulatory role in mitochondrial function by interacting with transcription factors such as YY1 and SIX5.

      Conclusions

      The expression patterns of lncRNA in women with PCOS were ascertained by microarray. Many lncRNA were differentially expressed in PCOS-T compared with PCOS-N, suggesting that they may play a key role in steroid genesis and metabolism.

      KEYWORDS

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      Biography

      Jin Li graduated from University of Luebeck and received her MD in 2012. She has been working as an assisted reproduction specialist since 2005. Her research interests include reproductive development and pathogenesis of polycystic ovary syndrome.