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Circ_0007121 Facilitates Trophoblastic Cell Proliferation, Migration, and Invasion via the Regulation of the miR-421/ZEB1 Axis in Preeclampsia

  • Reproductive Genetics: Original Article
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Abstract

Noncoding circular RNAs (circRNAs) have participated in the progression of preeclampsia (PE) via inhibiting microRNAs (miRNAs) to regulate gene expression. This study was designed to explore the miRNA/mRNA mechanism of hsa_circ_0007121 (circ_0007121) in PE. The expression detection of circ_0007121, microRNA-421 (miR-421), and zinc finger E-box binding homeobox 1 (ZEB1) was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. Transwell assay was used to determine cell migration and invasion. Cell apoptosis was evaluated using flow cytometry. The protein levels of epithelial-mesenchymal transition (EMT) markers and ZEB1 were measured via western blot. The interaction between miR-421 and circ_0007121 or ZEB1 was validated by dual-luciferase reporter assay. The expression detection indicated that circ_0007121 was downregulated in PE patients and the clinical data revealed that circ_0007121 was related to PE. The upregulation of circ_0007121 promoted cell proliferation, migration, invasion, and EMT in trophoblastic cells. Furthermore, circ_0007121 was identified as a sponge of miR-421 and the function of circ_0007121 was dependent on the sponge effect on miR-421. Moreover, ZEB1 was a target of miR-421 and circ_0007121/miR-421 axis could regulate the expression of ZEB1. In addition, miR-421 overexpression repressed trophoblastic cell behaviors through downregulating the ZEB1 level. Altogether, circ_0007121 contributed to the development of trophoblastic cells by regulating the miR-421/ZEB1 axis.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Obstetrics, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huai’an, 223300, Jiangsu, China

    Fenmei Zhou, Hongxue Liu & Yanlan Sun

  2. Department of Pathology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai, 223300, China

    Ruirui Zhang

Authors
  1. Fenmei Zhou
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  2. Hongxue Liu
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  3. Ruirui Zhang
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  4. Yanlan Sun
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Contributions

Yanlan Sun designed and supervised the study. Fenmei Zhou conducted the experiments and drafted the manuscript. Fenmei Zhou and Hongxue Liu collected and analyzed the data. Ruirui Zhang contributed the methodology and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yanlan Sun.

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Ethics Approval and Consent to Participate

The study was approved by the Ethics Committee of The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University. Written informed consents were obtained from all patients prior to study commencement.

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Not applicable.

Conflict of Interest

The authors declare no competing interests.

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Zhou, F., Liu, H., Zhang, R. et al. Circ_0007121 Facilitates Trophoblastic Cell Proliferation, Migration, and Invasion via the Regulation of the miR-421/ZEB1 Axis in Preeclampsia. Reprod. Sci. 29, 100–109 (2022). https://doi.org/10.1007/s43032-021-00713-0

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  • DOI: https://doi.org/10.1007/s43032-021-00713-0

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