Dataset Information

Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia.

ABSTRACT: In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing their surrounding vasculature network. Transformed cancer cells are known to exhibit phenotypic alterations, enabling continuous proliferation despite a limited oxygen supply. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines of the BJ model responded strikingly different to hypoxia. Besides corroborating many of the known responses to hypoxia, we demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response.

SUBMITTER: Danielsson F

PROVIDER: S-EPMC5929421 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia.

Danielsson Frida F Fasterius Erik E Sullivan Devin D Hases Linnea L Sanli Kemal K Zhang Cheng C Mardinoglu Adil A Al-Khalili Cristina C Huss Mikael M Uhlén Mathias M Williams Cecilia C Lundberg Emma E

Oncotarget 20180413 28

In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing their surrounding vasculature network. Transformed cancer cells are known to exhibit phenotypic alterations, enabling continuous proliferation despite a limited oxygen supply. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and mode ...[more]

PMID: 29731978

Similar Datasets

Project description:BackgroundThe key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, sparing the occipital region.ObjectivesTo identify biological differences among HF subpopulations.MethodsPaired vertex and occipital HFs from 10 male donors with AGA were collected for RNA sequencing assay. Furthermore, HF and cell experiments were conducted on the identified key genes to reveal their roles in AGA.ResultsTranscriptome profiles revealed that 506 mRNAs, 55 microRNAs and 127 long noncoding RNAs were differentially expressed in the AGA vertex HFs. Pathway analysis of mRNAs and microRNAs revealed involvement of the hypoxia-inducible factor (HIF)-1, Wnt/β-catenin, and focal adhesion pathways. Differential expression of HIF-1 prolyl hydroxylase enzymes (EGLN1, EGLN3) and Wnt/β-catenin pathway inhibitors (SERPINF1, SFRP2) was experimentally validated. In vitro studies revealed that reduction of EGLN1, EGLN3, SERPINF1 and SFRP2 stimulated proliferation of dermal papilla cells. Ex vivo HF studies showed that downregulation of EGLN1, EGLN3 and SERPINF1 promoted HF growth, postponed HF catagen transition, and prolonged the anagen stage, suggesting that these genes may be potentially utilized as therapeutic targets for AGA.ConclusionsWe characterized key transcriptome changes in male AGA HFs, and found that HIF-1 pathway-related genes (EGLN1, EGLN3) and Wnt pathway inhibitors (SERPINF1, SFRP2) may play important roles in AGA. What is already known about this topic? Multiple differentially expressed genes and signalling pathways have been found between hair follicles (HFs) in the balding area (frontal and vertex regions) and nonbalding area (occipital region) of individuals with androgenetic alopecia (AGA). A whole-transcriptome atlas of the vertex and occipital region is lacking. What does this study add? We identified a number of differentially expressed genes and pathways between balding vertex and nonbalding occipital AGA HFs by using whole-transcriptome analyses. We identified pathways not previously reported in AGA, such as the hypoxia-inducible factor (HIF)-1 signalling pathway. We verified that HIF-1 pathway-related genes (EGLN1, EGLN3) and Wnt pathway inhibitors (PEDF, SFRP2) played important roles in dermal papilla cell activity, hair growth and the hair cycle. What is the translational message? The EGLN1, EGLN3, SERPINF1 and SFRP2 genes may be potentially utilized as therapeutic targets for AGA.

Dataset Information

Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia.

Publications

Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets