The anti-proliferative effects of type I IFN involve STAT6-mediated regulation of SP1 and BCL6
| Autor: | Chi Chun Huang, Lei Wan, Yung Jen Kung, Ching Yao Chang, Yu An Hsu, Hui Ju Lin, Kuan Rong Lee |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Sp1 Transcription Factor 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation immune system diseases Neoplasms hemic and lymphatic diseases parasitic diseases Humans STAT2 Cell Proliferation B-Lymphocytes Gene knockdown Sp1 transcription factor integumentary system biology Cell growth Interferon-alpha STAT2 Transcription Factor respiratory system Molecular biology Chromatin DNA-Binding Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Cell culture Gene Knockdown Techniques Proto-Oncogene Proteins c-bcl-6 biology.protein Cancer research Signal transduction STAT6 Transcription Factor Signal Transduction 030215 immunology |
| Zdroj: | Cancer Letters. 375:303-312 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2016.02.047 |
| Popis: | Type I IFN-induced STAT6 has been shown to have anti-proliferative effects in Daudi and B cells. IFN-sensitive (DS) and IFN-resistant (DR) subclones of Daudi cells were used to study the role of STAT6 in the anti-proliferative activities. Type I IFN significantly increased STAT6 mRNA and protein expression in DS but not DR cells. STAT6 knockdown significantly reduced the sensitivity to IFN in both cell lines. The molecular targets and functional importance of IFN-activated STAT6 were performed by chromatin immunoprecipitation-on-chip (ChIP-on-chip) experiments in type I IFN-treated Daudi cells. Two target genes (Sp1 and BCL6) were selected from the ChIP-on-chip data. IFN-induced STAT6 activation led to Sp1 upregulation and BCL6 downregulation in DS cells, with only minimal effects in DR cells. siRNA inhibition of STAT6 expression resulted in decreased Sp1 and BCL6 mRNA and protein levels in both DS and DR cells. IFN treatment did not increase Sp1 and BCL6 expression in a STAT2-deficient RST2 cell line, and this effect was mitigated by plasmid overexpression of STAT2, indicating that STAT2 is important for STAT6 activation. These results suggest that STAT6 plays an important role in regulating Sp1 and BCL6 through STAT2 to exert the anti-proliferative effects of type I IFN. |
| Databáze: | OpenAIRE |
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