The Oncogenic Role of Yin Yang 1

Zhang, Qiang; Stovall, Daniel B.; Inoue, Kazushi; Sui, Guangchao

doi:10.1615/critrevoncog.v16.i3-4.30

Cited by 131 publications

(173 citation statements)

References 171 publications

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“…45), p27 (46), VEGF (33), and others (5,47). Thus, although the whole p53-dependent and -independent mechanisms of YY1 contribution to HIF-1a stabilization and tumorigenesis remains to be elucidated, our results showing that YY1 is associated with HIF-1a regulation under hypoxia further elucidated a novel important role of YY1 in tumor biology, and targeting YY1 might be a potential therapeutic strategy that might give consistent clinical outcomes independent of p53 status in cancer therapy.…”

Section: Discussionmentioning

confidence: 56%

Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner

Kasim

Kano

et al. 2013

Cancer Research

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In response to hypoxic stress, hypoxia-inducible factor (HIF)-1a is a critical transcription factor regulating fundamental cellular processes, and its elevated expression level and activity are associated with poor outcomes in most malignancies. The transcription factor Yin Yang 1 (YY1) is an important negative regulator of the tumor suppressor factor p53. However, the role of YY1 under tumor hypoxic condition is poorly understood. Herein, we show that inhibition of YY1 reduced the accumulation of HIF-1a and its activity under hypoxic condition, and consequently downregulated the expression of HIF-1a target genes. Interestingly, our results revealed that the downregulation of HIF-1a by inhibiting YY1 is p53-independent. Functionally, the in vivo experiments revealed that inhibition of YY1 significantly suppressed growth of metastatic cancer cells and lung colonization and also attenuated angiogenesis in a p53-null tumor. Collectively, our findings unraveled a novel mechanism by which YY1 inhibition disrupts hypoxia-stimulated HIF-1a stabilization in a p53-independent manner. Therefore, YY1 inhibition could be considered as a potential tumor therapeutic strategy to give consistent clinical outcomes independent of p53 status. Cancer Res; 73(6);

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Section: Discussionmentioning

confidence: 56%

Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner

Kasim

Kano

et al. 2013

Cancer Research

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“…The results show MNB1A, DOF2, PBF, YY1, PRRX2, UBX and ARNT-AHR are unique for the downregulated DEGs promoters, while GATA2, ZNF42, deltaEF1, MYCN and ARNT are unique for the upregulated DEG promoters. The transcription factor Yin Yang (YY) 1 is overexpressed in most cancers, regulating multiple cancer-related proteins and signaling pathways, and overexpression of YY1 both at mRNA and protein levels in ESCC tissue has been confirmed by Luo et al [29][30][31]. For other transcription factors that might respond to the upregulated DEGs, overexpression of Snail occurs in ESCC and correlates positively with lymphovascular invasion and was associated with worse overall survival [32].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analyses of m-RNA Profiling Following Ezrin Knockdown in Esophageal Squamous Cell Carcinoma

Xie¹

2014

J Cancer Sci Ther

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Ezrin is involves in multiple cancer cell functions. In this study, differentially expressed genes (DEGs) identified from mRNA expression profiling following Ezrin knockdown in esophageal squamous cell carcinoma (ESCC), were analyzed by multiple bioinformatics methods for a comprehensive understanding. Gene Ontology enrichment found significant terms related to immunity, stimulus response, extracellular matrix-binding and signal transduction. Functional Annotation Chart showed except GO categories, these DEGs were annotated by 72 functional category terms. Subpathway analyses revealed the DEGs were involved in 36 subpathways, overwhelming the traditional pathway enrichment. Promoter analyses showed specific sequence patterns and transcription factors correspond to the co-downregulation and co-upregulation of DEGs. MNB1A, DOF2, PBF, YY1, PRRX2, UBX and ARNT-AHR co-regulate the downregulated genes, whereas GATA2, ZNF42, deltaEF1, MYCN and ARNT co-regulate the upregulated genes. This paper provides a workflow for a better understanding the roles of Ezrin knockdown in ESCC by the bioinformatics analyses of its DEGs.

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“…Besides acting as a transcription factor, YY1 can also regulate gene expression without its DNA binding activity, by functioning as a co-factor and recruiting other regulators [30,32]. In this regard, the physical interactions between YY1 and R-Smads or Smad4 were found to interfere with Smad-DNA binding, impeding Smad transcriptional activities [37].…”

Section: Discussionmentioning

confidence: 99%

“…As a transcription factor/co-factor, YY1 and Smad7 can associate with histone deacetylases (HDACs) and regulate gene expression [22,24,31,32]. Therefore, we asked whether HDACs are involved in the synergy between YY1 and Smad7 in attenuating TGF-β signaling.…”

Section: Yy1 Synergizes With Nuclear Smad7 and Facilitates Its Transcmentioning

confidence: 99%

Yin Yang 1 (YY1) synergizes with Smad7 to inhibit TGF-β signaling in the nucleus

Yan

Pan

Xiong

et al. 2013

Sci. China Life Sci.

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As a prototype of the TGF-β superfamily cytokines, TGF-β is well known for its diverse roles in embryogenesis and adult tissue homeostasis. TGF-β evokes cellular responses by signaling mainly through cell membrane receptors and transcription factor R-Smads and Co-Smad (Smad4), while an inhibitory Smad, Smad7, acts as a critical negative regulator of TGF-β signaling. Smad7 antagonizes TGF-β signaling by regulating the stability or activity of the receptors or blocking the DNA binding of the functional R-Smad-Smad4 complex in the nucleus. However, the function of Smad7 in the nucleus is not fully understood. Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor with multiple functions. It has been reported that YY1 can inhibit Smad-dependent transcriptional responses and TGF-β/BMP-induced cell differentiation independently of its DNA binding ability. In this study, we found that Smad7 interacts with YY1 and the interaction is attenuated by TGF-β signaling. Reporter assays and target gene expression analyses revealed that Smad7 and YY1 act in concert to inhibit TGF-β-induced transcription in the nucleus. Furthermore, Smad7 could enhance the interaction of YY1 with the histone deacetylase HDAC1. Consistently, YY1 and HDAC1 augmented the transcription repression activity of Smad7 in Gal4-luciferase reporter analysis. Therefore, our findings define a novel mechanism of Smad7 and YY1 to antagonize TGF-β signaling.TGF-β, Smad7, YY1, HDAC1, signaling regulation, transcriptional co-repressor Citation:

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The Oncogenic Role of Yin Yang 1

Cited by 131 publications

References 171 publications

Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner

Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner

Bioinformatics Analyses of m-RNA Profiling Following Ezrin Knockdown in Esophageal Squamous Cell Carcinoma

Yin Yang 1 (YY1) synergizes with Smad7 to inhibit TGF-β signaling in the nucleus

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