组蛋白去乙酰化酶11的过表达抑制基底样乳腺癌细胞的侵袭和转移
[Overexpression of histone deacetylase 11 suppresses basal-like breast cancer cell invasion and metastasis].
作者信息
Yi Zhang, Wenwen Luo, Kun Wang, Jian Shi
机构信息
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Second Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2019 Jul 30;39(7):751-759. doi: 10.12122/j.issn.1673-4254.2019.07.01.
OBJECTIVE
Histone deacetylase 11 (HDAC11) is a class Ⅳ member of histone deacetylase family, and its role in regulating cancer cell invasion and metastasis remains unclear. We aimed to investigate the role of HDAC11 in regulating the biological behaviors of basal-like breast cancer (BLBC) cells.
METHODS
We analyzed the expression of HDAC11 based on Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). The effects of HDAC11 on the cell invasion and metastasis were examined using Transwell assay and in a mouse model. The interaction between HDAC11 and Twist was detected with immunoprecipitation. We identified 2 as a target gene of Twist using promoter luciferase assay and chromatin immunoprecipitation assay.
RESULTS
HDAC11 was lowly expressed in BLBC cells. HDAC11 overexpression suppressed BLBC cell invasion and their metastasis in nude mice. Mechanistically, HDAC11 directly interacted with Twist protein, antagonized its pro-invasive function and repressed Twist-induced 2 gene transcription.
CONCLUSION
Our data suggest that HDAC11 acts as a negative modulator of invasion and metastasis of BLBC cells.
目的
组蛋白去乙酰化酶11（HDAC11）是组蛋白去乙酰化酶家族的Ⅳ类成员，其在调节癌细胞侵袭和转移中的作用尚不清楚。我们旨在研究HDAC11在调节基底样乳腺癌（BLBC）细胞生物学行为中的作用。
方法
我们基于基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）分析了HDAC11的表达情况。使用Transwell实验和小鼠模型检测HDAC11对细胞侵袭和转移的影响。通过免疫沉淀检测HDAC11与Twist之间的相互作用。我们使用启动子荧光素酶实验和染色质免疫沉淀实验确定2为Twist的靶基因。
结果
HDAC11在BLBC细胞中低表达。HDAC11过表达抑制了BLBC细胞的侵袭及其在裸鼠中的转移。机制上，HDAC11直接与Twist蛋白相互作用，拮抗其促侵袭功能并抑制Twist诱导的2基因转录。
结论
我们的数据表明，HDAC11作为BLBC细胞侵袭和转移的负调节因子发挥作用。
Zotero 插件