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Series GSE90599 Query DataSets for GSE90599
Status Public on Jun 12, 2017
Title Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1α stabilization
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Solid tumors are less oxygenated than normal tissues, and for this reason the cancer cells have developed several molecular mechanisms of adaptation to hypoxic environment. Moreover, his poor oxygenation is a major indicator of an adverse prognosis and leads resistance to standard anticancer treatment. Previous reports from this laboratory showed an involvement of Che-1/AATF (Che-1) in cancer cell survival under stress conditions, and on the basis of these observations, we hypothesized that Che-1 might have a role in the response of cancer cells to hypoxia.
Methods: The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA, was subjected to normoxic and hypoxic conditions to perform studies about the role of this protein in metabolic adaptation and cell proliferation. The expression of Che-1 under normoxia or hypoxia was detected using western blot assays; cell metabolism was assessed by NMR spectroscopy and functional assays. Further molecular studies were performed by RNA seq, qRT-PCR and ChIP analysis.
Results: In this paper we report that Che-1 expression is required for the adaptation of the cells to hypoxia, playing and important role in metabolic modulation. Indeed, Che-1 depletion impacted on glycolysis by altering the expression of several genes involved in the response to hypoxia by modulating the levels of HIF-1alpha.
Conclusions: These data demonstrate a novel player in the regulation of a HIF1alpha in response to hypoxia. We found that the transcriptional down-regulation of a members of E3 ubiquitin ligase family SIAH2 by Che-1, produces a failure in the degradation by the hydroxylase PHD3 with a decrease in HIF-1alpha levels during hypoxia.
Overall design The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA was profiled for mRNA high-troughput sequencing (RNA-seq)
Contributor(s) Tiziana B, Matteo P, Maurizio F
Citation(s) 28214471
Submission date Nov 28, 2016
Last update date May 15, 2019
Contact name Matteo Pallocca
Organization name Italian National Cancer Institute "Regina Elena"
Street address Via Fermo Ognibene
City Rome
ZIP/Postal code 00144
Country Italy
Platforms (1)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
Samples (4)
GSM2407510 siControl
GSM2407511 SiChe-1
GSM2407512 siControl 4H Hypoxia
BioProject PRJNA356445
SRA SRP094652

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Supplementary file Size Download File type/resource
GSE90599_FPKM_table.tsv.gz 317.2 Kb (ftp)(http) TSV
GSE90599_RAW.tar 770.8 Mb (http)(custom) TAR (of BIGWIG)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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