ZNF384–ZEB1 feedback loop regulates breast cancer metastasis

Autor: Qing-Xiang Meng, Ke-Nie Wang, Jun-Hui Li, Hui Zhang, Zhao-Hui Chen, Xue-Jie Zhou, Xu-Chen Cao, Ping Wang, Yue Yu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular Medicine, Vol 28, Iss 1, Pp 1-13 (2022)
Druh dokumentu: article
ISSN: 1076-1551
1528-3658
DOI: 10.1186/s10020-022-00541-1
Popis: Abstract Background Breast cancer has become the most frequently diagnosed cancer worldwide. Increasing evidence indicated that zinc finger proteins (ZNFs), the largest family of transcription factors, contribute to cancer development and progression. Although ZNF384 is overexpressed in several types of human cancer, the role of ZNF384 in breast cancer remains unknown. Therefore, our research focused on ZNF384 regulation of the malignant phenotype of breast cancer and the underlying molecular mechanisms. Methods CCK-8 and colony formation assays were used to evaluate cell proliferation. Transwell and scratch assays were used to evaluate the cell migration and invasion. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were used to confirm the target relationship between ZNF384 and zinc finger E-box binding homeobox 1 (ZEB1). Xenografts were used to monitor the targets in vivo effects. Results We noted that ZNF384 was significantly overexpressed in breast cancer and highlighted the oncogenic mechanism of ZNF384. ZNF384 transactivated ZEB1 expression and induced an epithelial and mesenchymal-like phenotype, resulting in breast cancer metastasis. Furthermore, ZNF384 may be a target of miR-485-5p, and ZEB1 can up-regulate ZNF384 expression by repressing miR-485-5p expression. Together, we unveiled a feedback loop of ZNF384–ZEB1 in breast cancer metastasis. Conclusions The findings suggest that ZNF384 can serve as a prognostic factor and a therapeutic target for breast cancer patients.
Databáze: Directory of Open Access Journals
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