Wei Gong , Xin Zhu , Wenwu Zhang , Xiaoyu Song , Junjie Hu , Weihua Xu , Zhichao Ma , Bin Xiao , Linhai Li , Xinping Chen
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Considering the large heterogeneity of different breast cancer cells, we temporarily selected MCF-7 cell line for verification. In vitro overexpression experiments showed that overexpression of ZNF775 significantly inhibited the proliferation and migration of MCF-7 BC cell. We further combined RNA-sequencing (RNA-seq) and CUT & Tag, and found that overexpression of ZNF775 can down-regulate the expression of most genes in the Wnt signaling pathway. The cBioportal database showed that ZNF775 was negatively correlated with the expression of Wnt5a, suggesting that its downstream target was likely Wnt5a. Finally, we discovered that Wnt5a could partially reverse the inhibitory effect of ZNF775 on MCF-7 BC cell migration through transwell migration experiments. In conclusion, our findings will provide new ideas for the diagnosis, treatment and prognosis assessment of BC in the future.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"12 ","pages":"Article 100129"},"PeriodicalIF":2.0000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ZNF775 inhibits MCF-7 breast cancer cell migration by downregulating Wnt5a\",\"authors\":\"Wei Gong , Xin Zhu , Wenwu Zhang , Xiaoyu Song , Junjie Hu , Weihua Xu , Zhichao Ma , Bin Xiao , Linhai Li , Xinping Chen\",\"doi\":\"10.1016/j.adcanc.2024.100129\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>C2H2 zinc finger protein is widely involved in the occurrence and development of cancer. However, the function and mechanism of most C2H2 zinc finger proteins in breast caner (BC) remains unclear. Here, we reported the expression prognosis of C2H2 type zinc finger protein ZNF775 in BC patients and its possible biological mechanism. First, multiple public databases showed that ZNF775 was significantly overexpressed in BC tissues. Interestingly, high expression of ZNF775 was significantly associated with a better prognosis. Immunohistochemistry were used for verification, and the expression of ZNF775 was consistent with the databases. Considering the large heterogeneity of different breast cancer cells, we temporarily selected MCF-7 cell line for verification. In vitro overexpression experiments showed that overexpression of ZNF775 significantly inhibited the proliferation and migration of MCF-7 BC cell. We further combined RNA-sequencing (RNA-seq) and CUT & Tag, and found that overexpression of ZNF775 can down-regulate the expression of most genes in the Wnt signaling pathway. The cBioportal database showed that ZNF775 was negatively correlated with the expression of Wnt5a, suggesting that its downstream target was likely Wnt5a. Finally, we discovered that Wnt5a could partially reverse the inhibitory effect of ZNF775 on MCF-7 BC cell migration through transwell migration experiments. In conclusion, our findings will provide new ideas for the diagnosis, treatment and prognosis assessment of BC in the future.</div></div>\",\"PeriodicalId\":72083,\"journal\":{\"name\":\"Advances in cancer biology - metastasis\",\"volume\":\"12 \",\"pages\":\"Article 100129\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-10-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in cancer biology - metastasis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667394024000169\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in cancer biology - metastasis","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667394024000169","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
C2H2 锌指蛋白广泛参与癌症的发生和发展。然而,大多数 C2H2 型锌指蛋白在乳腺癌(BC)中的功能和机制仍不清楚。在此,我们报告了C2H2型锌指蛋白ZNF775在乳腺癌患者中的表达预后及其可能的生物学机制。首先,多个公共数据库显示ZNF775在BC组织中显著过表达。有趣的是,ZNF775的高表达与较好的预后明显相关。免疫组化法进行了验证,ZNF775的表达与数据库一致。考虑到不同乳腺癌细胞的异质性较大,我们暂时选择 MCF-7 细胞系进行验证。体外过表达实验表明,过表达 ZNF775 能显著抑制 MCF-7 BC 细胞的增殖和迁移。我们进一步结合 RNA 序列分析(RNA-seq)和 CUT & Tag,发现过表达 ZNF775 可下调 Wnt 信号通路中大部分基因的表达。cBioportal数据库显示,ZNF775与Wnt5a的表达呈负相关,表明其下游靶标可能是Wnt5a。最后,我们通过经孔迁移实验发现,Wnt5a 可以部分逆转 ZNF775 对 MCF-7 BC 细胞迁移的抑制作用。总之,我们的研究结果将为今后 BC 的诊断、治疗和预后评估提供新的思路。
ZNF775 inhibits MCF-7 breast cancer cell migration by downregulating Wnt5a
C2H2 zinc finger protein is widely involved in the occurrence and development of cancer. However, the function and mechanism of most C2H2 zinc finger proteins in breast caner (BC) remains unclear. Here, we reported the expression prognosis of C2H2 type zinc finger protein ZNF775 in BC patients and its possible biological mechanism. First, multiple public databases showed that ZNF775 was significantly overexpressed in BC tissues. Interestingly, high expression of ZNF775 was significantly associated with a better prognosis. Immunohistochemistry were used for verification, and the expression of ZNF775 was consistent with the databases. Considering the large heterogeneity of different breast cancer cells, we temporarily selected MCF-7 cell line for verification. In vitro overexpression experiments showed that overexpression of ZNF775 significantly inhibited the proliferation and migration of MCF-7 BC cell. We further combined RNA-sequencing (RNA-seq) and CUT & Tag, and found that overexpression of ZNF775 can down-regulate the expression of most genes in the Wnt signaling pathway. The cBioportal database showed that ZNF775 was negatively correlated with the expression of Wnt5a, suggesting that its downstream target was likely Wnt5a. Finally, we discovered that Wnt5a could partially reverse the inhibitory effect of ZNF775 on MCF-7 BC cell migration through transwell migration experiments. In conclusion, our findings will provide new ideas for the diagnosis, treatment and prognosis assessment of BC in the future.