ZIC2 is downregulated and represses tumor growth via the regulation of STAT3 in breast cancer
| Autor: | Ze‐Xian Liu, Xin An, Ting Yang, Yu‐Jie Liu, Yan-Min Liu, Yu Zhang, Qi Zhang, Qian Zhong, Shang-Xin Liu, Yi-Ling Luo, Man-Zhi Li, Bin-liu Liu, Ai Jun Zhou, Qian Liu, Zhi Hua Liu, Xue‐Min Liu, Mei Ling Chen |
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| Rok vydání: | 2019 |
| Předmět: |
STAT3 Transcription Factor
Cancer Research Small interfering RNA Down-Regulation Breast Neoplasms medicine.disease_cause 03 medical and health sciences Mice 0302 clinical medicine Breast cancer Downregulation and upregulation Cell Line Tumor Biomarkers Tumor Medicine Animals Humans Phosphorylation STAT3 Promoter Regions Genetic Transcription factor Cell Proliferation Gene knockdown biology business.industry Sequence Analysis RNA Nuclear Proteins medicine.disease Prognosis Gene Expression Regulation Neoplastic Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research biology.protein MCF-7 Cells Chromatin Immunoprecipitation Sequencing Female business Carcinogenesis Neoplasm Transplantation Signal Transduction Transcription Factors |
| Zdroj: | International journal of cancerReferences. 147(2) |
| ISSN: | 1097-0215 |
| Popis: | Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP-seq and RNA-seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation. |
| Databáze: | OpenAIRE |
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