2011
DOI: 10.1073/pnas.1019059108
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RA-inducible gene-I induction augments STAT1 activation to inhibit leukemia cell proliferation

Abstract: RA-inducible gene I (RIG-I/DDX58) has been shown to activate IFN-β promoter stimulator 1 (IPS-1) on recognizing cytoplasmic viral RNAs. It is unclear how RIG-I functions within the IFN and/or RA signaling process in acute myeloid leukemia (AML) cells, however, where obvious RIG-I induction is observed. Here, we show that the RIG-I induction functionally contributes to IFN-α plus RA-triggered growth inhibition of AML cells. Interestingly, although RIG-I induction itself is under the regulation of STAT1, a major… Show more

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Cited by 78 publications
(82 citation statements)
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“…RIG-I itself initially was identified as a protein involved in cell proliferation and differentiation (17). Many studies indicated that there were cross-talks between cell cycle regulation and immune response (18,19).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…RIG-I itself initially was identified as a protein involved in cell proliferation and differentiation (17). Many studies indicated that there were cross-talks between cell cycle regulation and immune response (18,19).…”
Section: Resultsmentioning
confidence: 99%
“…These findings prompted us to think about the possible crosstalk between RIG-I-mediated immune response and cell cycle regulation. In fact, it was reported that RIG-I itself was responsible for enhancing STAT1 activation to inhibit leukemia cell proliferation (17). A recent study showed that influenza A virus NS1 protein not Upon RNA virus infection, the RIG-I or TLR pathway is activated to promote the production of IFN-b.…”
Section: Discussionmentioning
confidence: 99%
“…We also demonstrated that human FLT3-ITD 1 AML samples had increased miR-155 and a decreased IFN gene expression signature when compared with FLT3-WT AML, which is consistent with our mouse data. It is well established that IFN signaling has growth-inhibitory effects on the hematopoietic compartment, [20][21][22][23] and inhibition of IFN signaling was recently discovered as a novel mechanism by which FLT3-ITD 1 cells can avoid the antiproliferative effects of IFN-a and IFN-g. 24 Our results indicate that miR-155 is clearly involved in this mechanism that subverts the antiproliferative effects of IFN in this setting. Our findings are also in line with a recent study demonstrating that miR-155 promotes proliferation of CD8 1 T cells through inhibition of IFN signaling, 34 indicating that this mechanism is used by multiple cell types in vivo.…”
Section: Flt3-wt Aml (mentioning
confidence: 99%
“…Mechanistically, we show that miR-155 inhibits the response to interferon (IFN) in these model systems, and this involves direct repression of Cebpb. Interferon has previously been shown to exhibit an antiproliferative effect on early hematopoietic cells, [20][21][22][23] including in our FLT3-ITD mouse model. 24 Altogether, our study identifies a specific role for miR-155 in promoting the expansion of myeloid cells in FLT3-ITD-mediated disease in vivo, indicating that inhibition of miR-155 may be a promising new therapeutic approach for treatment of FLT3-ITD 1 AML.…”
Section: Introductionmentioning
confidence: 99%
“…There is an Asp-Glu-x-His (DExH) box in amino acid alignment of MDA5 protein, and proteins with a DExH box encode RNA helicases that are involved in various biological reactions associated with RNA metabolism (Schwer 2001). Another DExH protein retinoic acid-inducible gene-I (RIG-I) was identified as a lipopolysaccharide-inducible gene in endothelial cells (Imaizumi et al 2002) and separately as a retinoic acid-inducible gene in leukemia cells (Jiang et al 2011). Recently, it was shown that MDA5 and RIG-I function as pathogen recognition receptors against viral doublestranded RNA (dsRNA) and these two molecules may play an important role in innate immune reactions against viral infection (Yoneyama et al 2005).…”
mentioning
confidence: 99%