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Disruption of ZNF334 promotes triple-negative breast carcinoma malignancy through the SFRP1/ Wnt/β-catenin signaling axis

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Abstract

Zinc-finger proteins (ZNFs) constitute the largest transcription factor family in the human genome. The family functions in many important biological processes involved in tumorigenesis. In our research, we identified ZNF334 as a novel tumor suppressor of triple-negative breast cancer (TNBC). ZNF334 expression was usually reduced in breast cancerv (BrCa) tissues and TNBC cell lines MDA-MB-231 (MB231) and YCCB1. We observed that promoter hypermethylation of ZNF334 was common in BrCa cell lines and tissues, which was likely responsible for its reduced expression. Ectopic expression of ZNF334 in TNBC cell lines MB231 and YCCB1 could suppress their growth and metastatic capacity both in vitro and in vivo, and as well induce cell cycle arrest at S phase and cell apoptosis. Moreover, re-expression of ZNF334 in TNBC cell lines could rescue Epithelial-Mesenchymal Transition (EMT) process and restrain stemness, due to up-regulation of SFRP1, which is an antagonist of Wnt/β-catenin signaling. In conclusion, we verified that ZNF334 had a suppressive function of TNBC cell lines by targeting the SFRP1/Wnt/β-catenin signaling axis, which might have the potentials to become a new biomarker for diagnosis and treatment of TNBC patients.

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Availability of data and material

Online analysis was performed using UALCAN (http://ualcan.path.uab.edu/ analysis.html) and Gepia2 (http://gepia2.cancer-pku.cn/#correlation) with the Cancer Genome Atlas (TCGA) database. Other data used in this study are available on reasonable request.

Abbreviations

ZNFs:

Zinc-finger proteins

TNBC:

Triple-negative breast cancer

BrCa:

Breast cancer

MB231:

MDA-MB-231

EMT:

Epithelial-Mesenchymal Transition (EMT)

PR:

Progesterone receptor

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor 2

KRAB-ZFPs:

Zinc-finger proteins containing a Kruppel associated box

FZD:

Frizzled

Aza:

5-Aza-2’-deoxycytidine

TSA:

Trichostatin A

MethylTarget:

Multiple targeted bisulfite enrichment sequencing

MSP:

Methylation-specific PCR

IHC:

Immunohistochemistry

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Acknowledgements

The authors thank Prof. Qian Tao (the Chinese University of Hong Kong, Hong Kong, China) for generously providing YCCB1 cell lines and TOP/FOP flash plasmids.

Funding

This study was supported by the National Natural Science Foundation of China (#81872380, #82172619), Natural Science Foundation of Chongqing (cstc2019jcjy-msxmX0861, cstc2020jcyj-bshX0025), Postdoctoral Science Foundation of China (2020M683262).

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  1. Zhaobo Cheng and Renjie Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Zhaobo Cheng, Renjie Yu, Yujia Liu, Xiangyi Zhou & Tingxiu Xiang

  2. Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Zhaobo Cheng, Renjie Yu, Li Li, Junhao Mu, Yijia Gong, Fan Wu & Ran Sun

  3. Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China

    Xiaohua Zeng, Yongzhong Wu & Tingxiu Xiang

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  1. Zhaobo Cheng
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Contributions

TX: conception and design. ZC, RY: performed majority of experiments. TX, LL, FW, JM: performed experiments and analyzed data. YL, XZ: collected samples. TX, ZC, RS: drafted the manuscript. TX, RS, XZ, YW: reviewed data and manuscript. TX, RS: reviewed data and finalized the manuscript. All authors reviewed and approved the final version.

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Correspondence to Ran Sun or Tingxiu Xiang.

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Cheng, Z., Yu, R., Li, L. et al. Disruption of ZNF334 promotes triple-negative breast carcinoma malignancy through the SFRP1/ Wnt/β-catenin signaling axis. Cell. Mol. Life Sci. 79, 280 (2022). https://doi.org/10.1007/s00018-022-04295-1

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