The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis

Fang, Xuefeng; Yoon, Jae-Geun; Li, Lisha; Yu, Wei; Shao, Jiaofang; Hua, Dasong; Zheng, Suiping; Hood, Leroy; Goodlett, David R.; Foltz, Gregory; Lin, Biaoyang

doi:10.1186/1471-2164-12-11

Cited by 137 publications

(146 citation statements)

References 56 publications

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“…In support of this view, chromatin immunoprecipitation-seq studies show that Sox2 can bind directly to the promoter of Dnmt3b [50,51], and a dramatic decrease of Zfp459 expression is observed after Sox2 knockout [52]. Our data also reveal that the methylation process begins immediately after Sox2 overexpression, while the induction of endogenous Nanog begins much later.…”

Section: Discussionsupporting

confidence: 78%

Two-Phase Analysis of Molecular Pathways Underlying Induced Pluripotent Stem Cell Induction

Lin

Perez

Lei³

et al. 2011

Stem Cells

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Induced pluripotent stem cells (iPSCs) can be reprogrammed from adult somatic cells by transduction with Oct4, Sox2, Klf4, and c-Myc, but the molecular cascades initiated by these factors remain poorly understood. Impeding their elucidation is the stochastic nature of the iPS induction process, which results in heterogeneous cell populations. Here we have synchronized the reprogramming process by a two-phase induction: an initial stable intermediate phase following transduction with Oct4, Klf4, and c-Myc, and a final iPS phase following overexpression of Sox2. This approach has enabled us to examine temporal gene expression profiles, permitting the identification of Sox2 downstream genes critical for induction. Furthermore, we have validated the feasibility of our new approach by using it to confirm that downregulation of transforming growth factor b signaling by Sox2 proves essential to the reprogramming process. Thus, we present a novel means for dissecting the details underlying the induction of iPSCs, an approach with significant utility in this arena and the potential for wide-ranging implications in the study of other reprogramming mechanisms. STEM

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Section: Discussionsupporting

confidence: 78%

Two-Phase Analysis of Molecular Pathways Underlying Induced Pluripotent Stem Cell Induction

Lin

Perez

Lei³

et al. 2011

Stem Cells

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“…6). Searching the promoter region of FN1 with SOX2 consensus binding motif, AA-CAA(A/T)G (Maruyama et al, 2005) or wwTGywTT (Fang et al, 2010), we identified two SOX2 binding sites that are located at -1950 and -3750 nucleotides upstream of the transcription start site of FN1 (data not shown). These data strongly confirmed that SOX2 directly regulates FN1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…We picked 20 SOX2 bound genes (Table 1), including fibronectin 1 (FN1), from our previous ChIP-seq analysis of SOX2 in glioblastoma multiforme (GBM) (Fang et al, 2011) and colorectal cancer cells (Fang et al, 2010). We found that FN1 and S100P are the two most significantly induced genes by SOX2, when comparing the SOX2 overexpressing clones with the mock controls (Fig.…”

Section: Sox2 Targets Fibronectin 1 To Promote Cell Migration and Invmentioning

confidence: 99%

SOX2 Targets Fibronectin 1 to Promote Cell Migration and Invasion in Ovarian Cancer: New Molecular Leads for Therapeutic Intervention

Lou

Han

Jin

et al. 2013

OMICS: A Journal of Integrative Biology

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Ovarian cancer ranks as the second most common tumor of the female reproductive system, with a large burden on global public health. Therefore, the identification of novel molecular targets and diagnostics is an urgent need for many women affected by this disease. To this end, the human transcription factor SOX2 is involved in a wide range of pathophysiological roles, such as the maintenance of stem cell characteristics and carcinogenesis. To date, in most studies, SOX2 has been shown to promote the development of cancer, although its inhibitory roles in cancer have also been reported. However, to the best of our knowledge, the role of SOX2, specifically in ovarian cancer cells, has not been examined in detail. In this article, we report, for the first time, that SOX2 promotes migration, invasion, and clonal formation of ovarian cancer cells. We further observed that SOX2 targeted FN1, a key gene that regulates cell migration in ovarian cancer. Our findings collectively suggest that the SOX2-FN1 axis is a key pathway in mediating the migration and invasion of ovarian cancer cells. This pathway offers crucial molecular insights and promises to develop putative candidate therapeutic interventions in women with ovarian cancer.

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“…Studies of miR-21 expression in cancer stem cells (CSCs) (Bao et al 2011;Bao et al 2012;Han et al 2012) have placed miR-21 in the early stages of tumor development, as CSCs have the ability to self-renew and generate the various cells comprising the tumor (Reya et al 2001;Visvader 2011). Indeed, it has been reported that miR-21 may play an important role in CSCs of various tumor types (Bao et al 2011;Bao et al 2012;Han et al 2012) but the results have been ambiguous concerning brain tumors (Fang et al 2011;Ma et al 2012;Põlajeva et al 2012). Difficulties in the precise molecular characterization of CSCs using immunohistochemical (IHC) markers may contribute to the poor reproducibility and lack of consensus among published studies (Hermansen et al 2011;Dahlrot et al 2013) and this suggests that several markers should be applied for the identification of CSCs in situ.…”

mentioning

confidence: 99%

miR-21 Is Linked to Glioma Angiogenesis

Hermansen

Nielsen

Aaberg-Jessen

et al. 2015

J Histochem Cytochem.

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MicroRNA-21 (miR-21) is the most consistently over-expressed microRNA (miRNA) in malignant gliomas. We have previously reported that miR-21 is upregulated in glioma vessels and subsets of glioma cells. To better understand the role of miR-21 in glioma angiogenesis and to characterize miR-21-positive tumor cells, we systematically stained consecutive serial sections from ten astrocytomas for miR-21, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), phosphatase and tensin homolog (PTEN), octamer-binding transcription factor 4 (Oct4), sex-determining region Y box 2 (Sox2) and CD133. We developed an image analysis-based co-localization approach allowing global alignment and quantitation of the individual markers, and measured the miR-21 in situ hybridization signal against the immunohistochemical staining of the six different markers. miR-21 significantly co-localized with the hypoxia- and angiogenesis-associated markers HIF-1α (p=0.0020) and VEGF (p=0.0096), whereas the putative miR-21 target, PTEN, was expressed independently of miR-21. Expression of stem cell markers Oct4, Sox2 and CD133 was not associated with miR-21. In six glioblastoma cultures, miR-21 did not correlate with the six markers. These findings suggest that miR-21 is linked to glioma angiogenesis, that miR-21 is unlikely to regulate PTEN, and that miR-21-positive tumor cells do not possess stem cell characteristics.

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The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis

Cited by 137 publications

References 56 publications

Two-Phase Analysis of Molecular Pathways Underlying Induced Pluripotent Stem Cell Induction

Two-Phase Analysis of Molecular Pathways Underlying Induced Pluripotent Stem Cell Induction

SOX2 Targets Fibronectin 1 to Promote Cell Migration and Invasion in Ovarian Cancer: New Molecular Leads for Therapeutic Intervention

miR-21 Is Linked to Glioma Angiogenesis

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