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miR-526b-5p/c-Myc/Foxp1 participates in recurrent spontaneous abortion by regulating the proliferation, migration, and invasion of trophoblasts

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

Abstract

Purpose

As a member of the C19MC family, miR-526b-5p is mainly expressed in the placental tissue and is a well-known tumor suppressor microRNA. However, its effect on the function of trophoblasts and its role in the development of recurrent spontaneous abortion (RSA) remains unclear.

Methods

Transcriptome sequencing, quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, 5-ethynyl-2′-deoxyuridine (Edu) proliferation analysis, cell counting kit-8 (CCK8) assay, Transwell assays, and wound healing were used to detect the proliferation, migration, and invasion capacity of trophoblasts. Target genes of miR-526b-5p were obtained by the dual luciferase reporter system. The promoter-reporter system and ChIP-qPCR were used to prove that c-Myc positively regulated the expression of Foxp1

Results

The miR-526b-5p levels were significantly higher in patients with RSA than in controls. High expression of miR-526b-5p inhibited the proliferation, migration, and invasion of trophoblast cell line. By contrast, low expression of miR-526b-5p promoted the proliferation and migration of trophoblast cell line. Target genes of miR-526b-5p were c-Myc and Foxp1. c-Myc positively regulated the expression of Foxp1 by binding to the Foxp1 promoter location -146/-135. Finally, miR-526b-5p impeded the proliferation, migration, and invasion of trophoblasts by negatively regulating c-Myc by rescue experiments.

Conclusion

Thus, miR-526b-5p affected the proliferation, migration, and invasion of trophoblasts by targeting c-Myc and Foxp1. Low expression of c-Myc further deactivated the positive transcriptional regulation of c-Myc on Foxp1, which may be the mechanism of RSA. This study provides potential therapeutic targets and clues for the diagnosis and treatment of RSA.

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Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

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Funding

This study is supported by Chongqing Postdoctoral Science Foundation (cstc2021jcyj-bsh0068), Chongqing Postdoctoral Research Special Funding Project (2021XM3100), and the National Natural Science Foundation of China (82171664).

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Author notes

  1. Li Luo and Lu Yao contributed equally to this work.

Authors and Affiliations

  1. Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, No. 1 Yixueyuan Rd, Chongqing, 400016, China

    Li Luo, Lu Yao, Youlong Xie & Luxing Ge

  2. Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, No. 120, Longshan Rd, Chongqing, 401147, China

    Li Luo, Lu Yao & Yubin Ding

  3. Department of Genetics, School of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China

    Enxiang Chen

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  1. Li Luo
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  2. Lu Yao
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  3. Youlong Xie
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  4. Enxiang Chen
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  6. Luxing Ge
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Correspondence to Luxing Ge.

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The medical ethics committee approved the study of Chongqing Medical University and the First Affiliated Hospital of Chongqing Medical University (Reference Number: 2022138).

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Luo, L., Yao, L., Xie, Y. et al. miR-526b-5p/c-Myc/Foxp1 participates in recurrent spontaneous abortion by regulating the proliferation, migration, and invasion of trophoblasts. J Assist Reprod Genet 40, 1559–1572 (2023). https://doi.org/10.1007/s10815-023-02793-0

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  • DOI: https://doi.org/10.1007/s10815-023-02793-0

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