title: EZH2 depletion blocks the proliferation of colon cancer cells.
abstract: The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi)-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer.
authors.affiliation: Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center, DKFZ, Heidelberg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Fussbroich
authors.forename: Nina
authors.initials: N
authors.lastname: Wagener
authors.forename: Stephan
authors.initials: S
authors.lastname: Macher-Goeppinger
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Maria
authors.initials: M
authors.lastname: Fälth
authors.forename: Holger
authors.initials: H
authors.lastname: Sültmann
authors.forename: Angela
authors.initials: A
authors.lastname: Holzer
authors.forename: Karin
authors.initials: K
authors.lastname: Hoppe-Seyler
authors.forename: Felix
authors.initials: F
authors.lastname: Hoppe-Seyler
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D016193:G1 Phase; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D063151:Polycomb Repressive Complex 2; D034622:RNA Interference; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2