Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication.
Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication.
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DOI：
10.1186/s13046-016-0359-2
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发表时间：
2016-05-25
期刊：
影响因子：
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通讯作者：
Bonavida B
中科院分区：
文献类型：
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作者：
Kaufhold S;Garbán H;Bonavida B
与正常组织相比，转录因子阴阳1 （YY1）在癌组织中经常过表达，在细胞增殖、细胞活力、上皮-间质转化、转移和药物/免疫抵抗中具有调节作用。YY1与癌症干细胞（CSCs）具有许多共同的特性，这些特性驱动肿瘤发生、转移和耐药，并受某些转录因子的过表达调节，包括SOX2、OCT4 （POU5F1）、BMI1和NANOG。基于这些相似性，我们预计YY1的表达可能与SOX2、OCT4、BMI1和NANOG的表达和活性有关。来自Human Protein Atlas的基于蛋白质组学组织的数据集的数据挖掘用于YY1和四种CSC标记物在17种癌症（包括实体和血液恶性肿瘤）中的蛋白质表达模式。在所分析的所有肿瘤中，发现YY1和SOX2以及SOX2和OCT4的表达频率密切相关。根据YY1和SOX2之间的关联性质，确定了两种类型的动力学，即逆或正。这两种动态定义了BMI1和OCT4表达的不同模式。根据YY1和SOX2表达以及BMI1和OCT4表达的关系，将肿瘤分为四组，并具有不同的分子特征：1)前列腺癌、肺癌、宫颈癌、子宫内膜癌、卵巢癌和胶质瘤（YY1loSOX2hiBMI1hiOCT4hi）； 2)皮肤、睾丸和乳腺癌（YY1hiSOX2loBMI1hiOCT4hi）； 3)肝脏、胃、肾、胰腺和尿路上皮癌（YY1loSOX2loBMI1hiOCT4hi）； 4)结直肠癌、淋巴瘤和黑色素瘤（YY1hiSOX2hiBMI1loOCT4hi）。我们提出了NF-kB/PI3K/AKT通路与下游靶基因产物YY1、OCT4、SOX2和BMI1的相互调控相互作用的调控环。本文的在线版本（doi:10.1186/s13046-016-0359-2）包含补充材料，可供授权用户使用。
The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal transition, metastasis and drug/immune resistance. YY1 shares many properties with cancer stem cells (CSCs) that drive tumorigenesis, metastasis and drug resistance and are regulated by overexpression of certain transcription factors, including SOX2, OCT4 (POU5F1), BMI1 and NANOG. Based on these similarities, it was expected that YY1 expression would be associated with SOX2, OCT4, BMI1, and NANOG’s expressions and activities. Data mining from the proteomic tissue-based datasets from the Human Protein Atlas were used for protein expression patterns of YY1 and the four CSC markers in 17 types of cancer, including both solid and hematological malignancies. A close association was revealed between the frequency of expressions of YY1 and SOX2 as well as SOX2 and OCT4 in all cancers analyzed. Two types of dynamics were identified based on the nature of their association, namely, inverse or direct, between YY1 and SOX2. These two dynamics define distinctive patterns of BMI1 and OCT4 expressions. The relationship between YY1 and SOX2 expressions as well as the expressions of BMI1 and OCT4 resulted in the classification of four groups of cancers with distinct molecular signatures: 1) Prostate, lung, cervical, endometrial, ovarian and glioma cancers (YY1loSOX2hiBMI1hiOCT4hi) 2) Skin, testis and breast cancers (YY1hiSOX2loBMI1hiOCT4hi) 3) Liver, stomach, renal, pancreatic and urothelial cancers (YY1loSOX2loBMI1hiOCT4hi) and 4) Colorectal cancer, lymphoma and melanoma (YY1hiSOX2hiBMI1loOCT4hi). A regulatory loop is proposed consisting of the cross-talk between the NF-kB/PI3K/AKT pathways and the downstream inter-regulation of target gene products YY1, OCT4, SOX2 and BMI1. The online version of this article (doi:10.1186/s13046-016-0359-2) contains supplementary material, which is available to authorized users.