A let-7/Fas double-negative feedback loop regulates human colon carcinoma cells sensitivity to Fas-related apoptosis
► Let-7/Fas form a double-negative feedback loop which regulates Fas-mediated apoptosis. ► Fas activation suppresses Dicer processing and let-7 microRNA biogenesis. ► Let-7 inhibitor sensitizes colon carcinoma cells to Fas-related apoptosis. Interferon-γ (IFN-γ) is considered essential for the regul...
Saved in:
Published in | Biochemical and biophysical research communications Vol. 408; no. 3; pp. 494 - 499 |
---|---|
Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
13.05.2011
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | ► Let-7/Fas form a double-negative feedback loop which regulates Fas-mediated apoptosis. ► Fas activation suppresses Dicer processing and let-7 microRNA biogenesis. ► Let-7 inhibitor sensitizes colon carcinoma cells to Fas-related apoptosis.
Interferon-γ (IFN-γ) is considered essential for the regulation of anti-tumor reactions as it sensitizes Fas-related apoptosis in HT29 cells, but the mechanism is unclear. In the current study, our data demonstrated that IFN-γ stimulation and Fas activation suppressed Dicer processing and let-7 microRNA biogenesis, while let-7 microRNA strongly inhibited Fas expression by directly targeting Fas mRNA. Accordingly, our results indicate that Fas and let-7 microRNAs form a double-negative feedback loop in IFN-γ and Fas induced apoptosis in colon carcinoma cell line HT29, which may be an important synergistic mechanism in anti-tumor immune response. We also found that a let-7 microRNA inhibitor increased Fas expression and sensitized cells to Fas-related apoptosis, which may have future implications in colon carcinoma therapy. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2011.04.074 |