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FOXN4通过直接激活P53抑制乳腺癌进展。

FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53.

作者信息

Ye Hui, Duan Meiling

机构信息

Department of Galactophore, Linyi Central Hospital of Shandong, Linyi, People's Republic of China.

Department of Respiratory One, Linyi Central Hospital of Shandong, Linyi, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jan 7;13:71-81. doi: 10.2147/OTT.S206775. eCollection 2020.

DOI:10.2147/OTT.S206775
PMID:32021256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6954834/
Abstract

BACKGROUND

Fork head domain-containing gene family (Fox) transcription factors, consisting of over 20 members, are involved in the progression of certain types of tumor. However, whether FOXN4 is involved in carcinogenesis and tumor progression is still unclear.

PURPOSE

In this study, we investigated the clinicopathological significance and the underlying mechanism of FOXN4 in breast cancer.

METHODS AND RESULTS

We examined the lower expression of FOXN4 in breast cancer tissues and cancer cell lines. The expression of FOXN4 is negatively correlated with tumor size and lymph node metastasis. Using CCK-8 assay, colony formation assay, wound healing assay, and Transwell assay, we revealed that FOXN4 notably decreased breast cancer cell proliferation, epithelial-mesenchymal transition and invasion in vitro. In addition, quantitative chromatin immunoprecipitation and luciferase assays determined that FOXN4 was able to directly bind with the promoter of P53. RT-qPCR and Western blotting analysis showed that FOXN4 could directly activate P53 expression. Functionally, P53 knockdown rescued the tumor inhibition effects of FOXN4 in breast cancer cells.

CONCLUSION

The present study provides new insights into the role of FOXN4 in breast cancer progression and suggests FOXN4 might represent a potential therapeutic target in breast cancer by modulating P53.

摘要

背景

包含叉头结构域的基因家族（Fox）转录因子由20多个成员组成，参与某些类型肿瘤的进展。然而，FOXN4是否参与肿瘤发生和肿瘤进展仍不清楚。

目的

在本研究中，我们调查了FOXN4在乳腺癌中的临床病理意义及其潜在机制。

方法与结果

我们检测了乳腺癌组织和癌细胞系中FOXN4的低表达。FOXN4的表达与肿瘤大小和淋巴结转移呈负相关。使用CCK-8检测、集落形成检测、伤口愈合检测和Transwell检测，我们发现FOXN4在体外显著降低乳腺癌细胞的增殖、上皮-间质转化和侵袭。此外，定量染色质免疫沉淀和荧光素酶检测确定FOXN4能够直接与P53的启动子结合。RT-qPCR和蛋白质免疫印迹分析表明FOXN4可以直接激活P53的表达。在功能上，P53基因敲低挽救了FOXN4对乳腺癌细胞的肿瘤抑制作用。

结论

本研究为FOXN4在乳腺癌进展中的作用提供了新的见解，并表明FOXN4可能通过调节P53代表乳腺癌的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/bc816c5e9b04/OTT-13-71-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/f693a10f4d4f/OTT-13-71-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/f55b5a53d0bf/OTT-13-71-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/b04dcb36dba1/OTT-13-71-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/5bdd79bcd030/OTT-13-71-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/c694cf64b76a/OTT-13-71-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/bc816c5e9b04/OTT-13-71-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/f693a10f4d4f/OTT-13-71-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/f55b5a53d0bf/OTT-13-71-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/b04dcb36dba1/OTT-13-71-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/5bdd79bcd030/OTT-13-71-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/c694cf64b76a/OTT-13-71-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03be/6954834/bc816c5e9b04/OTT-13-71-g0006.jpg

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本文引用的文献

1
FOXN2 is downregulated in breast cancer and regulates migration, invasion, and epithelial- mesenchymal transition through regulation of SLUG.FOXN2在乳腺癌中表达下调，并通过调控SLUG来调节迁移、侵袭和上皮-间质转化。
Cancer Manag Res. 2019 Jan 4;11:525-535. doi: 10.2147/CMAR.S176938. eCollection 2019.
2
Downregulation of FOXO6 in breast cancer promotes epithelial-mesenchymal transition and facilitates migration and proliferation of cancer cells.乳腺癌中FOXO6的下调促进上皮-间质转化并促进癌细胞的迁移和增殖。
Cancer Manag Res. 2018 Oct 30;10:5145-5156. doi: 10.2147/CMAR.S157661. eCollection 2018.
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Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway.
野生型 p53 通过 GAS7-CYFIP1 介导的信号通路上调早期乳腺癌相关基因 GAS7 以抑制转移。
Oncogene. 2018 Jul;37(30):4137-4150. doi: 10.1038/s41388-018-0253-9. Epub 2018 Apr 30.
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Development. 2016 Dec 15;143(24):4558-4570. doi: 10.1242/dev.112672.
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