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SNORA71B 通过诱导上皮-间充质转化促进乳腺癌细胞穿过血脑屏障。

SNORA71B promotes breast cancer cells across blood-brain barrier by inducing epithelial-mesenchymal transition.

机构信息

Department of Breast Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Mingde Road, Donghu District, Nanchang, 330006, Jiangxi Province, China.

Medical College of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China.

出版信息

Breast Cancer. 2020 Nov;27(6):1072-1081. doi: 10.1007/s12282-020-01111-1. Epub 2020 May 23.

DOI:10.1007/s12282-020-01111-1
PMID:32458152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7567732/
Abstract

BACKGROUND

Brain metastasis (BM) is a dreadful complication that significantly impacts the quality of life in breast cancer patients. A key process during brain metastasis is the migration of cancer cells across blood-brain barrier (BBB). However, the role of snoRNAs regulating BBB in BM is still unknown.

METHODS

Here SNORic and GEO databases were used to identify differentially expressed snoRNAs between brain metastatic and non-metastatic breast cancer (BC) tissues. The effects of SNORA71B on the capacities of proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and BBB invasion of BC cells were evaluated by CCK8, transwell, western blot, and BBB model, respectively.

RESULTS

SNORA71B was highly expressed in high BM BC tissues and cells compared to low BM BC controls. Survival analysis revealed high expression of SNORA71B was significantly associated with poor PPS and OS in breast cancer patients. ROC curve showed that SNORA71B might act as biomarker for breast cancer. Moreover, SNORA71B significantly promoted proliferation, migration, and invasion of BC cells with different BM abilities. Importantly, SNORA71B promoted the EMT process of low BM BC cells. SNORA71B knockdown inhibited the high BM BC cells across BBB, while EMT activator dramatically abrogated this inhibited effect.

CONCLUSIONS

In conclusion, SNORA71B promotes BC cells across the BBB partly via inducing EMT.

摘要

背景

脑转移（BM）是乳腺癌患者生活质量的严重并发症。癌细胞穿过血脑屏障（BBB）是脑转移的关键过程。然而，snoRNAs 调节 BM 中 BBB 的作用仍不清楚。

方法

本研究使用 SNORic 和 GEO 数据库鉴定脑转移和非脑转移乳腺癌（BC）组织中差异表达的 snoRNAs。通过 CCK8、transwell、western blot 和 BBB 模型分别评估 SNORA71B 对 BC 细胞增殖、迁移、侵袭、上皮间质转化（EMT）和 BBB 侵袭能力的影响。

结果

与低 BM BC 对照组相比，高 BM BC 组织和细胞中 SNORA71B 表达水平较高。生存分析显示，SNORA71B 高表达与乳腺癌患者的较差 PPS 和 OS 显著相关。ROC 曲线表明 SNORA71B 可能作为乳腺癌的生物标志物。此外，SNORA71B 显著促进了不同 BM 能力的 BC 细胞的增殖、迁移和侵袭。重要的是，SNORA71B 促进了低 BM BC 细胞的 EMT 过程。SNORA71B 敲低抑制了高 BM BC 细胞穿过 BBB，而 EMT 激活剂则显著消除了这种抑制作用。

结论

总之，SNORA71B 通过诱导 EMT 促进 BC 细胞穿过 BBB。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/d50ed894aafa/12282_2020_1111_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/5f7991f4c117/12282_2020_1111_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/5edb91938e01/12282_2020_1111_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/db16a05e92c2/12282_2020_1111_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/d3b9a5057bcc/12282_2020_1111_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/f25a2008ab7d/12282_2020_1111_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/d50ed894aafa/12282_2020_1111_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/5f7991f4c117/12282_2020_1111_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/5edb91938e01/12282_2020_1111_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/db16a05e92c2/12282_2020_1111_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/d3b9a5057bcc/12282_2020_1111_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/f25a2008ab7d/12282_2020_1111_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/7567732/d50ed894aafa/12282_2020_1111_Fig6_HTML.jpg

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