ArticleMolecular cancer research : MCR2012
Reduced DICER1 elicits an interferon response in endometrial cancer cells.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers.Oncotarget · 2014Trial
- PD-L1 Expression is Mediated by microRNA Processing, Wnt/β-Catenin Signaling, and Chemotherapy in Wilms Tumor.Pediatric blood & cancer · 2025Article
- Article
- Crosstalk Between Mammalian Antiviral Pathways.Non-coding RNA · 2019Review
- DICER1: A Key Player in Rheumatoid Arthritis, at the Crossroads of Cellular Stress, Innate Immunity, and Chronic Inflammation in Aging.Frontiers in immunology · 2018Review
- Inhibition of PI3K-AKT-mTOR pathway sensitizes endometrial cancer cell lines to PARP inhibitors.BMC cancer · 2017Article
- Article
- Article
- ARF and p53 coordinate tumor suppression of an oncogenic IFN-β-STAT1-ISG15 signaling axis.Cell reports · 2014Article
- MicroRNAs: The Missing Link in the Biology of Graft-Versus-Host Disease?Frontiers in immunology · 2013Review
- Glycogen synthase kinase 3β inhibition as a therapeutic approach in the treatment of endometrial cancer.International journal of molecular sciences · 2013Article
- Dicer represses the interferon response and the double-stranded RNA-activated protein kinase pathway in mouse embryonic stem cells.The Journal of biological chemistryArticle
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
DICER1 is essential for the generation of mature miRNAs and other short noncoding RNAs. Several lines of investigation implicate DICER1 as a tumor suppressor. Reduced DICER1 levels and changes in miRNA abundance have been associated with aggressive tumor phenotypes. The global effects of reduced DICER1 on mRNA transcript abundance in tumor cells remain largely unknown. We used short hairpin RNA to stably knock down DICER1 in endometrial cancer cell lines to begin to determine how reduced DICER1 activity contributes to tumor phenotypes. DICER1 knockdown did not affect cell proliferation but caused enhanced cell migration and growth in soft agar. miRNA and mRNA profiling in KLE cells revealed overall decreases in miRNA levels and changes in the relative abundance of many mRNAs. One of the most striking changes in mRNA levels was the upregulation of IFN-stimulated genes (ISG), the majority of which lack known miRNA target sequences. IFNβ, a key upstream regulator of the IFN response, was significantly increased in DICER1 knockdowns in the AN3CA, Ishikawa, and KLE endometrial cancer cell lines and in the normal endometrial cell line EM-E6/E7/TERT. IFNβ secreted in media from KLE and EM-E6/E7/TERT shDcr cells was sufficient to activate an IFN response in HT29 cells. The reduced miRNA processing in DICER1 knockdowns was associated with increases in pre-miRNAs in the cytoplasm. Our findings suggest that elevated pre-miRNA levels trigger the IFN response to double-stranded RNA. We thus report a novel effect of reduced DICER1 function in cancer cells.
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Registered trials
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