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CircRNA (circ)_0007823 Contributes to Triple-Negative Breast Cancer Progression and Cisplatin Resistance via the miR-182-5p/FOXO1 Pathway

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Abstract

Cisplatin (DDP) is used for the clinical management of triple-negative breast cancer (TNBC). However, the development of drug resistance limits its therapeutic efficacy. Circular RNAs (circRNAs) are known to be involved in tumor DDP resistance. In our previous study, we reported that circ_0007823 expression is downregulated and correlated with adverse prognosis in TNBC. However, its association with DDP resistance remains unclear. This study aimed to determine the role of circ_0007823 and miR-182-5p in DDP-resistant TNBC and explore the underlying mechanisms. First, expression profiles circ_0007823, microRNA (miR)-182-5p, and forkhead box O1 (FOXO1) in TNBC cells were determined. Additionally, biological characteristics of cells, including apoptosis, cell cycle, proliferation, and migration, were analyzed using various assays. Luciferase reporter and rescue assays were used to determine the correlations among circ_0007823, miR-182-5p, and FOXO1 expression. MiR-182-5p was overexpressed in DDP-resistant TNBC cells. MiR-182-5p knockdown suppressed the invasiveness and increased the apoptosis of drug-resistant cells, contributing to G1 arrest and S phase reduction. Mechanistically, circ_0007823 targeted miR-182-5p, and its overexpression drastically reduced the promotional effects of the miR-182-5p mimic on the aggression and transfer ability of drug-resistant cells. Furthermore, FOXO1 overexpression increased the sensitivity of cells to DDP and reduced their malignant progression. Therefore, FOXO1 was established as the downstream target of miR-182-5p that may be used to treat DDP-resistant TNBC. In summary, circ_0007823 overexpression attenuated DDP resistance in TNBC via the miR-182-5p–FOXO1 axis, indicating the therapeutic potential of circ_0007823 DDP-resistant TNBC treatment.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by Shanghai Municipal Health Commission (No. 202040144) and Changning Maternity and Infant Health Hospital (No. 2021Y-16). The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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  1. Haofeng Wang and Xiaojie Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Breast Surgery, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, No. 786, Yuyuan Road, Changning District, Shanghai, 200050, China

    Haofeng Wang, Weida Shen, Jing Cui & Jinling Yu

  2. Department of Pathology, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, 200050, China

    Xiaojie Wang & Yingzi Zhou

  3. Department of Laboratory, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, 200050, China

    Haichuan Li

Authors
  1. Haofeng Wang
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  4. Yingzi Zhou
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Contributions

All authors contributed to the study conception and design. HW, XW, WS, YZ, JC, HL, JY: Material preparation, data collection and analysis were performed. HW, XW: The first draft of the manuscript was written. HW, JY: Funding was obtained. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jinling Yu.

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Wang, H., Wang, X., Shen, W. et al. CircRNA (circ)_0007823 Contributes to Triple-Negative Breast Cancer Progression and Cisplatin Resistance via the miR-182-5p/FOXO1 Pathway. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10783-9

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