MilliporeSigma
  • Home
  • Search Results
  • Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER.

Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER.

Nature communications (2014-10-30)
Twan van den Beucken, Elizabeth Koch, Kenneth Chu, Rajesha Rupaimoole, Peggy Prickaerts, Michiel Adriaens, Jan Willem Voncken, Adrian L Harris, Francesca M Buffa, Syed Haider, Maud H W Starmans, Cindy Q Yao, Mircea Ivan, Cristina Ivan, Chad V Pecot, Paul C Boutros, Anil K Sood, Marianne Koritzinsky, Bradly G Wouters
ABSTRACT

MicroRNAs are small regulatory RNAs that post transcriptionally control gene expression. Reduced expression of DICER, the enzyme involved in microRNA processing, is frequently observed in cancer and is associated with poor clinical outcome in various malignancies. Yet, the underlying mechanisms are not well understood. Here we identify tumour hypoxia as a regulator of DICER expression in large cohorts of breast cancer patients. We show that DICER expression is suppressed by hypoxia through an epigenetic mechanism that involves inhibition of oxygen-dependent H3K27me3 demethylases KDM6A/B and results in silencing of the DICER promoter. Subsequently, reduced miRNA processing leads to derepression of the miR-200 target ZEB1, stimulates the epithelial to mesenchymal transition and ultimately results in the acquisition of stem cell phenotypes in human mammary epithelial cells. Our study uncovers a previously unknown relationship between oxygen-sensitive epigenetic regulators, miRNA biogenesis and tumour stem cell phenotypes that may underlie poor outcome in breast cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-trimethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit
Millipore
Cycloheximide solution, 0.1%, suitable for microbiology
Hydrocortisone for peak identification, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Cycloheximide solution, Ready-Made Solution, microbial, 100 mg/mL in DMSO, Suitable for cell culture
Progesterone, European Pharmacopoeia (EP) Reference Standard
Hydrocortisone, European Pharmacopoeia (EP) Reference Standard
Hydrocortisone, British Pharmacopoeia (BP) Assay Standard
Progesterone for system suitability, European Pharmacopoeia (EP) Reference Standard
Progesterone for peak identification, European Pharmacopoeia (EP) Reference Standard
Supelco
Progesterone, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Progesterone, United States Pharmacopeia (USP) Reference Standard
USP
Hydrocortisone, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Cycloheximide, Biotechnology Performance Certified
Supelco
Hydrocortisone, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Actinomycin D, from Streptomyces sp., suitable for cell culture, ≥95%
Sigma-Aldrich
Actinomycin D, from Streptomyces sp., ~98% (HPLC)
Sigma-Aldrich
Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
Progesterone, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Progesterone, meets USP testing specifications
Sigma-Aldrich
Progesterone, ≥99%
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Sigma-Aldrich
Progesterone, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
Actinomycin D, from Streptomyces sp., ≥95% (HPLC)
Sigma-Aldrich
Cycloheximide, from microbial, ≥94% (TLC)
Supelco
Cycloheximide, PESTANAL®, analytical standard
Supelco
Progesterone, VETRANAL®, analytical standard
Sigma-Aldrich
Cycloheximide, ≥95% (HPLC)