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PLAGL2 increases adriamycin resistance and EMT in breast cancer cells by activating the Wnt pathway

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Abstract

Background

Adriamycin (ADR) is an effective treatment for breast cancer; nevertheless, it is often linked with acquired resistance in breast cancer cells, reducing ADR’s therapeutic efficacy and increasing the risk of recurrence and poor prognosis. It has been revealed that the zinc-finger transcription factor pleomorphic adenoma gene like-2 (PLAGL2) is required for epithelial to mesenchymal transition (EMT) in cancer cells. Recent data indicates that PLAGL2 is also involved in regulating chemotherapeutic drug resistance, albeit the exact mechanism by which this happens remains unknown.

Objective

This study examines the effect of PLAGL2 on adriamycin resistance and EMT in breast cancer cells.

Methods

The small interfering RNA (siRNA) targeting PLAGL2 was transfected to breast cancer cells to alter PLAGL2 expression. Cell counting kit-8 (CCK-8) and colony formation assay detected cell growth and proliferation rate. Moreover, wound-healing and transwell assays were conducted to evaluate migration and invasion. Western blot (WB) checked the apoptosis and EMT-associated proteins.

Results

PLAGL2 expression is associated with breast cancer cells’ acquired resistance to ADR in this investigation. Additionally, deletion of PLAGL2 was associated with enhanced sensitivity to ADR, reduced proliferation, migration, and invasion capabilities, increased E-cadherin levels, and reduced Wnt6, β-catenin, and DVL1 levels in ADR-resistant breast cancer cells (MCF-7/ADR and MDA-MB-231/ADR cells). PLAGL2 could bind to the promoter region of Wnt6 and promote its expression. Additionally, the results of this research established that Wnt signaling is implicated in breast cancer cells’ resistance to ADR since BML-284, a Wnt signaling activator partly restored the sensitivity of MCF-7/ADR and MDA-MB-231/ADR cells to ADR.

Conclusion

PLAGL2 promotes adriamycin resistance and cell aggressiveness in breast cancer cells via activating the Wnt signaling pathway.

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Data availability

The data of this paper is available from the corresponding author on reasonable request.

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Funding

This work has been financially supported by the Department of Pharmaceutical Administration, National Health Commission.

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Authors and Affiliations

  1. Department of Basic Teaching, Zhuhai Campus of Zunyi Medical University, 368 Jinwan Road, Zhuhai, 519041, Guangdong, China

    Yuxiao Li, Xingzhao Han & Yahui Liu

  2. College of Basic Medicine, Hebei Medical University, Shijiazhuang, 050000, China

    Ruolin Liu

  3. Business School of International Medicine, China Pharmaceutical University, Nanjing, 210009, China

    Wei Xu

Authors
  1. Yuxiao Li
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  2. Ruolin Liu
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  3. Xingzhao Han
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  4. Wei Xu
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  5. Yahui Liu
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Contributions

YL and YL: conceived and designed the research; YL, RL, XH and WX: performed the experiments and analyzed the data. YL: wrote the manuscript. All authors read, commented, and accepted the final version.

Corresponding author

Correspondence to Yahui Liu.

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Yuxiao Li, Ruolin Liu, Xingzhao Han, Wei Xu and Yahui Liu declare that they have no conflict of interest.

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Li, Y., Liu, R., Han, X. et al. PLAGL2 increases adriamycin resistance and EMT in breast cancer cells by activating the Wnt pathway. Genes Genom 45, 49–57 (2023). https://doi.org/10.1007/s13258-022-01330-0

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  • DOI: https://doi.org/10.1007/s13258-022-01330-0

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