过表达组蛋白去乙酰基酶11抑制基底样乳腺癌细胞的侵袭和转移（英文）

Overexpression of histone deacetylase 11 suppresses basal-like breast cancer cell invasion and metastasis

目的研究组蛋白去乙酰基酶11(HDAC11)在基底样乳腺癌(BLBC)细胞侵袭和转移中的调控作用。方法利用GEO和TCGA数据库分析了HDAC11在BLBC中的表达,并用Transwell实验和裸鼠模型研究HDAC11对BLBC细胞侵袭和转移的影响。使用免疫共沉淀的方法观察HDAC11与Twist蛋白的相互结合,用启动子报告基因和染色体免疫共沉淀的方法鉴定HAS2是否为Twist的靶基因。结果与其他乳腺癌亚型相比,HDAC11在基底样乳腺癌中的表达较低。在BLBC细胞中过表达HDAC11可以强烈抑制BLBC细胞的体外迁移、侵袭和在裸鼠体内转移。HDAC11识别并占据Twist蛋白的DNA结合域,对抗其促侵袭的功能,并抑制Twist诱导的HAS2基因转录。结论 HDAC11过表达可抑制BLBC细胞的侵袭和转移。

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 amousemodel. The interaction between HDAC11 and Twist was detected with immunoprecipitation. We identified HAS2 as a target gene of Twist using promoter luciferase assay and chromatin immunoprecipitation assay. Results HDAC11was lowly expressed in BLBC cells.HDAC11 overexpression suppressed BLBC cell invasion in vitro and theirmetastasis in nude mice. Mechanistically, HDAC11 directly interacted with Twist protein, antagonized its pro-invasive function and repressed Twist-induced HAS2 gene transcription. Conclusion Our data suggest that HDAC11 acts as a negative modulator of invasion and metastasis of BLBC cells.