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Comprehensive analysis of lncRNA-miRNA-mRNA ceRNA network and key genes in granulosa cells of patients with biochemical primary ovarian insufficiency

  • Reproductive physiology and disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Primary ovarian insufficiency (POI) is a common condition leading to the pathological decline of ovarian function in women of reproductive age, resulting in amenorrhea, hypogonadism, and infertility. Biochemical premature ovarian insufficiency (bPOI) is an intermediate stage in the pathogenesis of POI in which the fertility of patients has been reduced. Previous studies suggest that granulosa cells (GCs) play an essential role in the pathogenesis of POI, but their pathogenetic mechanisms remain unclear. To further explore the potential pathophysiological mechanisms of GCs in POI, we constructed a molecular long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network using GC expression data collected from biochemical premature ovarian failure (bPOI) patients in the GEO database. We discovered that the GCs of bPOI patients had differential expression of 131 mRNAs, 191 lncRNAs, and 28 miRNAs. By systematic network analysis, we identified six key genes, including SRSF1, PDIA5, NEURL1B, UNK, CELF2, and CFL2, and five hub miRNAs, namely hsa-miR-27a-3p, hsa-miR-24-3p, hsa-miR-22-3p, hsa-miR-129-5p, and hsa-miR-17-5p, and the results suggest that the expression of these key genes may be regulated by two hub miRNAs, hsa-miR-27a-3p and hsa-miR-17-5p. Additionally, a POI model in vitro was created to confirm the expression of a few important genes. In this study, we discovered a unique lncRNA-miRNA-mRNA network based on the ceRNA mechanism in bPOI for the first time, and we screened important associated molecules, providing a partial theoretical foundation to better understand the pathogenesis of POI.

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Data availability

The datasets generated and analyzed during the current study are available in the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) database (Accession Number: GSE135697, GSE100238).

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Acknowledgements

This work was supported by the Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, and Tongji University. The results published here are in whole or partly based on data obtained from the Gene expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).

Funding

This project was supported by the National Nature Science Foundation of China (NO. 31900522).

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  1. Biting Liu and Li Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, China

    Biting Liu, Li Liu, Zubaidan Sulaiman, Chunyan Wang, Lian Wang, Jihui Zhu, Shupeng Liu & Zhongping Cheng

  2. Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai, 200072, China

    Li Liu, Lian Wang, Jihui Zhu, Shupeng Liu & Zhongping Cheng

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  1. Biting Liu
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Contributions

BL and LL contributed equally to this work. BL and LL contributed to the idea of the manuscript, completed the experiment, analyzed the data, and wrote this manuscript. BL and LL completed the revision of the manuscript. ZS, CW, JZ, and LW helped interpret the data. ZC and SL conceived the study. All authors read and approved the manuscript. BL and LL contributed equally to this work.

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Correspondence to Shupeng Liu or Zhongping Cheng.

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Liu, B., Liu, L., Sulaiman, Z. et al. Comprehensive analysis of lncRNA-miRNA-mRNA ceRNA network and key genes in granulosa cells of patients with biochemical primary ovarian insufficiency. J Assist Reprod Genet 41, 15–29 (2024). https://doi.org/10.1007/s10815-023-02937-2

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