Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer

ABSTRACT: Aberrant transcription of the HSATII pericentromeric satellite repeat is present in a wide variety of epithelial cancers. We observed that HSATII expression is induced in colon cancer cells cultured as xenografts or under non-adherent conditions in vitro, but it is rapidly lost in standard 2D cultures. Unexpectedly, physiological induction of endogenous HSATII RNA, as well as introduction of synthetic HSATII transcripts, generate complementary DNA intermediates in the form of DNA:RNA hybrids. Single molecule sequencing of tumor xenografts shows that HSATII RNA-derived DNA (rdDNA) molecules are stably reincorporated within pericentromeric loci, leading to progressive expansion of these regions We analyzed the dynamics of HSATII RNA and DNA level changes using single molecule sequencing (Helicos/SeqLL) in SW620 colon cancer cells transitioned from 2D in vitro culture conditions to growth as mouse xenografts and vice versa.

ORGANISM(S): Homo sapiens

SUBMITTER: Ben Wittner

PROVIDER: E-GEOD-64471 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer

Project description:Aberrant transcription of the HSATII pericentromeric satellite repeat is present in a wide variety of epithelial cancers. We observed that HSATII expression is induced in colon cancer cells cultured as xenografts or under non-adherent conditions in vitro, but it is rapidly lost in standard 2D cultures. Unexpectedly, physiological induction of endogenous HSATII RNA, as well as introduction of synthetic HSATII transcripts, generate complementary DNA intermediates in the form of DNA:RNA hybrids. Single molecule sequencing of tumor xenografts shows that HSATII RNA-derived DNA (rdDNA) molecules are stably reincorporated within pericentromeric loci, leading to progressive expansion of these regions

2015-11-02 | GSE64471 | GEO

WTX interacts with the transcriptional regulator TRIM28 to mediate cellular differentiation

Project description:WTX encodes a tumor suppressor implicated in Wilms tumor and in mesenchymal differentiation, with distinct functions in the cytoplasm, at the plasma membrane and in the nucleus. Here we report that the transcriptional corepressor TRIM28 is the major binding partner for nuclear WTX. The WTX-TRIM28 interaction supports chromatin binding by TRIM28, enhancing transcriptional silencing of some TRIM28 target sequences. In mouse ES cells, where TRIM28-mediated silencing of repetitive sequences is best characterized, Wtx knockdown similarly derepresses endogenous retroviruses and LINE elements. We performed digital gene expression (DGE) profiling using Helicos RNA sequencing. Helicos sequencing does not involve an amplification step, hence it has less bias, especially in sequencing of repetitive elements. We sequenced RNA extracted from mouse ESCs harboring GFP, Wtx or Trim28 hairpins. The resulting sequence reads were aligned with the RefSeq database as well as Repbase, which is a database for the repetitive sequences.

2015-04-16 | E-GEOD-60418 | biostudies-arrayexpress

Histone H3.3 maintains genome integrity during mammalian development

Project description:Histone H3.3 is a highly conserved histone H3 replacement variant in metazoans, and has been implicated in many important biological processes including cell differentiation and reprogramming. Germline and somatic mutations in H3.3 genomic incorporation pathway components, or in H3.3 encoding genes, have been associated with human congenital diseases and cancers, respectively. However, the role of H3.3 in mammalian development remains unclear. To address this question, we generated H3.3 null mouse models through classical genetic approaches. We found H3.3 plays an essential role in mouse development. Complete depletion of H3.3 leads to developmental retardation and early embryonic lethality. At the cellular level, H3.3 loss triggers cell cycle suppression and cell death. Surprisingly, H3.3 depletion does not dramatically disrupt gene regulation in the developing embryo. Instead, H3.3 depletion causes dysfunction of heterochromatin structures at telomeres, centromeres and pericentromeric regions of chromosomes leading to mitotic defects. The resulting karyotypical abnormalities and DNA damage lead to p53 pathway activation. In summary, our results reveal that an important function of H3.3 is to support chromosomal heterochromatic structures, thus maintaining genome integrity during mammalian development. RNA-seq in embryos at E10.5 comparing 3 samples with the following genotype Trp53-/-; H3f3afl/-; H3f3bfl/-; Sox2-CreTg/0 to three samples with the following genotype Trp53-/-; H3f3afl/+; H3f3bfl/+; Sox2-CreTg/0

2015-06-12 | E-GEOD-69771 | biostudies-arrayexpress

RNA sequencing of circulating tumour cells implicates WNT signaling in pancreatic cancer metastasis

Project description:This SuperSeries is composed of the following subset Series: GSE40171: RNA sequencing of circulating tumour cells implicates WNT signaling in pancreatic cancer metastasis (mouse data) GSE40174: RNA sequencing of circulating tumour cells implicates WNT signaling in pancreatic cancer metastasis (human data) Refer to individual Series

2012-08-17 | E-GEOD-40176 | biostudies-arrayexpress

RNA sequencing of circulating tumour cells implicates WNT signaling in pancreatic cancer metastasis (mouse data)

Project description:Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as enriched in CTCs. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. The effect of Wnt2 is correlated with fibronectin upregulation, and it is mediated in part through non-canonical Wnt signaling and suppressed by inhibition of the Map3k7 (Tak1) kinase, an integrator of Wnt, BMP and TGF-beta signaling. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple Wnt genes, and pancreatic CTCs revealed significant enrichment for non-canonical Wnt signaling in 5 of 11 cases. Thus, molecular analysis of CTCs may identify novel therapeutic targets to prevent the distal spread of cancer. Expression profiling of primary tumor, circulating tumor cells and ascites in a mouse model of pancreatic cancer suggested WNT signaling plays a role in pancreatic cancer metastasis. Induction of Wnt2 signaling in mouse pancreatic NB508 cells supported the hypothesis.

2012-08-17 | E-GEOD-40171 | biostudies-arrayexpress

RNA sequencing of circulating tumour cells implicates WNT signaling in pancreatic cancer metastasis (human data)

Project description:Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single-molecule RNA sequencing, identifying Wnt2 as enriched in CTCs. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. The effect of Wnt2 is correlated with fibronectin upregulation, and it is mediated in part through non-canonical Wnt signaling and suppressed by inhibition of the Map3k7 (Tak1) kinase, an integrator of Wnt, BMP and TGF-beta signaling. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple Wnt genes, and pancreatic CTCs revealed significant enrichment for non-canonical Wnt signaling in 5 of 11 cases. Thus, molecular analysis of CTCs may identify novel therapeutic targets to prevent the distal spread of cancer. Expression profiling of circulating tumor cells in human pancreatic cancer patients support a hypothesis that WNT signaling plays a role in pancreatic cancer metastasis.

2012-08-17 | E-GEOD-40174 | biostudies-arrayexpress

Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Cell Composition

Project description:By applying RNA-ISH and RNAseq to circulating tumor cells (CTCs), the study provides definitive evidence of epithelial to mesenchymal transition (EMT) across all histological types of breast cancer, identifying mediators such as FOXC1 and TGF-β signaling, and demonstrating dynamic treatment-associated changes in EMT within clusters of CTCs. Epithelial to mesenchymal transition (EMT) has been postulated to contribute to the migration and dissemination of cancer cells, but supporting histopathological evidence is limited. We used a microfluidic device to isolate circulating tumor cells (CTCs), combined with multiplex fluorescent RNA-in-situ hybridization (ISH) and RNA sequencing, to quantify and characterize EMT in breast cancer cells within the bloodstream. Whereas only rare (0.1-10%) cells in the primary tumor expressed both mesenchymal and epithelial markers, such biphenotypic as well as purely mesenchymal cells were enriched among CTCs, across all histological subtypes of breast cancer. In an index patient followed longitudinally, fluctuation in epithelial and mesenchymal states was observed as a function of initial response and subsequent resistance to therapy. Mesenchymal markers were predominant in clusters of tumor cells, many of which had adherent platelets. Finally, RNA sequencing of CTC clusters identified TGF-β and other EMT-related signatures, which were absent from more epithelial CTCs. FOXC1, a known regulator of EMT, was abundantly expressed in mesenchymal CTCs and was detectable within localized regions of the primary breast tumor. Together, these data support a role for EMT in the blood-borne dissemination of breast cancer and point to the dynamic nature of this cell fate change.

2013-02-01 | E-GEOD-41245 | biostudies-arrayexpress

RNASeq profiling of AZD8186-treated HCC70 xenografts

Project description:HCC70 xenografts treated with 11 doses of AZD8186 (100mg/kg BID) were compared to DMSO-treated control xenografts

2017-11-01 | E-MTAB-4656 | biostudies-arrayexpress

Transcription profiling of human PEGylated interferon-a2b treatment of one sensitive and two resistant osteosarcoma xenografts established in nude mice

Project description:Gene expression changes as a response to PEGylated interferon-a2b treatment of one sensitive and two resistant osteosarcoma xenografts established in nude mice

2010-04-12 | E-TABM-707 | biostudies-arrayexpress

RNA seq of a pancreatic cancer patient-derived xenografts treated with Vehicle or Gemcitabine/Paclitaxel in mouse

Project description:Identification of regulated genes in Patient-derived xenografts from pancreatic cancer

2023-03-21 | E-MTAB-11739 | biostudies-arrayexpress