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SAFB2 Inhibits the Progression of Breast Cancer by Suppressing the Wnt/β-Catenin Signaling Pathway via NFAT5

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Abstract

Aberrant scaffold attachment factor-B2 (SAFB2) expression is associated with several malignant tumors. In this study, we investigated how SAFB2 worked in the process of breast cancer as well as the underlying mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were used to investigate the expression of SAFB2 and nuclear factor of activated T cells 5 (NFAT5). Cellular proliferative ability was detected with cell counting kit 8 (CCK8), colony formation and 5-Ethynyl-2′-deoxyuridine (EdU) staining assays. Cell apoptosis was measured via flow cytometry and western blotting analysis. Wound healing, transwell assays, and western blotting analysis were executed to estimate cell migration and invasion. The relationship between SAFB2 and NFAT5 was verified by RNA immunoprecipitation (RIP) assay and NFAT5 mRNA stability was examined with actinomycin (Act) D assay. Western blotting analysis also tested the expression of Wnt/β-catenin signaling-associated proteins. As a result, SAFB2 was downregulated in breast cancer cell lines, while NFAT5 was highly expressed in most breast cancer cell lines. Overexpression of SAFB2 suppressed the proliferation, migration, and invasion while exacerbated the apoptosis of breast cancer cells. SAFB2 interacted with NFAT5 mRNA and declined the stability of NFAT5 mRNA. Overexpression of NFAT5 counteracted anti-proliferative, anti-metastatic and pro-apoptotic effects of SAFB2 in breast cancer cells. Mechanistically, SAFB2 overexpression inhibited the Wnt/β-catenin signaling pathway, while this effect was partially eliminated by NFAT5. Collectively, SAFB2 hindered breast cancer development and inactivated Wnt/β-catenin signaling via regulation of NFAT5, suggesting that SAFB2 might be a promising therapeutic target for breast cancer.

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Data Availability

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

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Authors and Affiliations

  1. Department of Breast Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 99 Longcheng Street, Taiyuan, 030032, Shanxi Province, China

    Huifen Zhen, Yarong Yao & Haibo Yang

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  1. Huifen Zhen
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  2. Yarong Yao
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  3. Haibo Yang
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Contributions

HZ and HY made substantial contributions to the conception and design of the study. HZ, YY, and HY performed experiments, drafted and revised the manuscript for important intellectual content. HZ and HY confirm the authenticity of the raw data. All authors read and approved the final manuscript.

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Correspondence to Haibo Yang.

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Zhen, H., Yao, Y. & Yang, H. SAFB2 Inhibits the Progression of Breast Cancer by Suppressing the Wnt/β-Catenin Signaling Pathway via NFAT5. Mol Biotechnol 65, 1465–1475 (2023). https://doi.org/10.1007/s12033-022-00649-z

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  • DOI: https://doi.org/10.1007/s12033-022-00649-z

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