HIST1H1B Promotes Basal-Like Breast Cancer Progression by Modulating CSF2 Expression.
HIST1H1B Promotes Basal-Like Breast Cancer Progression by Modulating CSF2 Expression.
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DOI：
10.3389/fonc.2021.780094
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发表时间：
2021
影响因子：
4.7
通讯作者：
Dong C
中科院分区：
文献类型：
--
作者：
Liao R;Chen X;Cao Q;Wang Y;Miao Z;Lei X;Jiang Q;Chen J;Wu X;Li X;Li J;Dong C
基底细胞样乳腺癌(BLBC)临床预后较差，但其侵袭性机制尚不清楚。已有研究表明，连接物组蛋白在肿瘤中对基因表达具有正向或负向调节作用。本研究旨在探讨HIST1H1B基因在BLBC发生发展中的可能作用及其机制。我们分析了多个基因表达数据集，以确定HIST1H1B表达与BLBC的相关性。我们利用实时定量聚合酶链式反应、Transwell实验、克隆形成实验和乳房实验分析了与HIST1H1B在乳腺癌中表达相关的分子事件。我们用芯片技术研究了HIST1H1B与CSF2的相关性。通过肿瘤发生实验，我们确定了HIST1H1B表达对BLBC细胞致瘤性的影响。在这里，我们发现连接蛋白HIST1H1B在BLBC中显著升高，这是由于HIST1H1B拷贝数扩增和启动子低甲基化。HIST1H1B通过结合克隆刺激因子2(CSF2)启动子上调CSF2的表达。HIST1H1B表达促进，而HIST1H1B表达下调则抑制致瘤性。在乳腺癌患者中，HIST1H1B的表达与肿瘤体积大、分级高、有无转移、生存不良呈正相关。HIST1H1B通过调节CSF2的表达促进基底细胞样乳腺癌的进展，提示HIST1H1B是一种潜在的预后标志物和治疗靶点。
Basal-like breast cancer (BLBC) is associated with a poor clinical outcome; however, the mechanism of BLBC aggressiveness is still unclear. It has been shown that a linker histone functions as either a positive or negative regulator of gene expression in tumors. Here, we aimed to investigate the possible involvement and mechanism of HIST1H1B in BLBC progression. We analyzed multiple gene expression datasets to determine the relevance of HIST1H1B expression with BLBC. We employed quantitative real-time PCR, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the expression of HIST1H1B in human breast cancer. We studied the association of HIST1H1B with CSF2 by ChIP assay. Using tumorigenesis assays, we determine the effect of HIST1H1B expression on tumorigenicity of BLBC cells. Here, we show that the linker histone HIST1H1B is dramatically elevated in BLBC due to HIST1H1B copy number amplification and promoter hypomethylation. HIST1H1B upregulates colony-stimulating factor 2 (CSF2) expression by binding the CSF2 promoter. HIST1H1B expression promotes, whereas knockdown of HIST1H1B expression suppresses tumorigenicity. In breast cancer patients, HIST1H1B expression is positively correlated with large tumor size, high grade, metastasis and poor survival. HIST1H1B contributes to basal-like breast cancer progression by modulating CSF2 expression, indicating a potential prognostic marker and therapeutic target for this disease.
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影响因子：
12.8
作者：
Hong IS
通讯作者：
Hong IS
抑制 UGT8 通过减弱硫苷脂-α V β 5 轴抑制基底样乳腺癌进展
DOI：
10.1084/jem.20172048
发表时间：
2018-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cao Q;Chen X;Wu X;Liao R;Huang P;Tan Y;Wang L;Ren G;Huang J;Dong C
通讯作者：
Dong C
影响因子：
64.8
作者：
ALLAN, J;HARTMAN, PG;AVILES, FX
通讯作者：
AVILES, FX
影响因子：
11.2
作者：
Liu W;Sun J;Li G;Zhu Y;Zhang S;Kim ST;Sun J;Wiklund F;Wiley K;Isaacs SD;Stattin P;Xu J;Duggan D;Carpten JD;Isaacs WB;Grönberg H;Zheng SL;Chang BL
通讯作者：
Chang BL
影响因子：
158.5
作者：
van de Vijver, MJ;He, YD;Bernards, R
通讯作者：
Bernards, R