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miR-101-5p suppresses trophoblast cell migration and invasion via modulating the DUSP6-ERK1/2 axis in preeclampsia

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

Abstract

Purpose

Dysregulated behaviors of trophoblast cells leading to defective placentation are considered the main cause of preeclampsia (PE). Abnormal miRNA expression profiles have been observed in PE placental tissue, indicating the significant role of miRNAs in PE development. This study aimed to investigate the expression of miR-101-5p in PE placental tissue and its biological functions.

Methods

The expression of miR-101-5p in placental tissue was detected by quantitative real-time PCR (qRT-PCR). The localization of miR-101-5p in term placental tissue and decidual tissue was determined by the fluorescence in situ hybridization (FISH)-immunofluorescence (IF) double labeling assay. The effect of miR-101-5p on the migration, invasion, proliferation, and apoptosis of the HTR8/SVneo trophoblast cells was investigated. Online databases combined with transcriptomics were used to identify potential target genes and related pathways of miR-101-5p. Finally, the interaction between miR-101-5p and the target gene was verified by qRT-PCT, WB, dual-luciferase reporter assay, and rescue experiments.

Results

The study found that miR-101-5p was upregulated in PE placental tissue compared to normal controls and was mainly located in various trophoblast cell subtypes in placental and decidual tissues. Overexpression of miR-101-5p impaired the migration and invasion of HTR8/SVneo cells. DUSP6 was identified as a potential downstream target of miR-101-5p. The expression of miR-101-5p was negatively correlated with DUSP6 expression in HTR8/SVneo cells, and miR-101-5p directly bound to the 3′ UTR region of DUSP6. DUSP6 upregulation rescued the migratory and invasive abilities of HTR8/SVneo cells in the presence of miR-101-5p overexpression. Additionally, miR-101-5p downregulated DUSP6, resulting in enhanced ERK1/2 phosphorylation.

Conclusion

This study revealed that miR-101-5p inhibits the migration and invasion of HTR8/SVneo cells by regulating the DUSP6-ERK1/2 axis, providing a new molecular mechanism for the pathogenesis of PE.

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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 work was supported by the National Natural Science Foundation of China (No. 82171668, No. 81771614, No. 82171662, No. 81901506, No. 82001581) and Joint Funds of the National Natural Science Foundation of China (No. U21A20346).

Author information

Author notes

  1. Jiacheng Xu and Jie Wang have contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, China

    Jiacheng Xu, Jie Wang, Miaomiao Chen, Bingdi Chao, Jie He, Yuxiang Bai, Hongli Liu, Lumei Xie, Yuelan Tao, Hongbo Qi & Xin Luo

  2. Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China

    Jiacheng Xu, Jie Wang, Bingdi Chao, Jie He, Hongli Liu, Lumei Xie, Yuelan Tao, Hongbo Qi & Xin Luo

  3. Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei Province, China

    Miaomiao Chen

  4. Reproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Xiaofang Luo

  5. Women and Children’s Hospital of Chongqing Medical University, Chongqing, China

    Hongbo Qi

Authors
  1. Jiacheng Xu
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Contributions

Conceptualization: Jiacheng Xu; methodology: Jiacheng Xu; investigation: Jiacheng Xu, Jie Wang, Miaomiao Chen; software: Bingdi Chao, Jie He; writing-original draft: Jiacheng Xu; writing-review and editing: Jie Wang; Xin Luo; funding acquisition: Yuxiang Bai, Xiaofang Luo, Xin Luo; formal analysis: Hongli Liu, Lumei Xie; validation: Yuelan Tao; supervision: Hongbo Qi, Xin Luo.

Corresponding authors

Correspondence to Hongbo Qi or Xin Luo.

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Xu, J., Wang, J., Chen, M. et al. miR-101-5p suppresses trophoblast cell migration and invasion via modulating the DUSP6-ERK1/2 axis in preeclampsia. J Assist Reprod Genet 40, 1597–1610 (2023). https://doi.org/10.1007/s10815-023-02846-4

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  • DOI: https://doi.org/10.1007/s10815-023-02846-4

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