title: 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 IFN intracellular signal mediator, under circumstances in which it does not stimulate IPS-1, it conversely augments STAT1 activation to induce IFN-stimulatory gene expression and inhibit leukemia cell proliferation. Thus, our results unveil a previously undescribed RIG-I activity in regulating the cellular proliferation of leukemia cells via STAT1, which is independent of its classic role of sensing viral invasion to trigger type I IFN transcription.
authors.affiliation: State Key Laboratory for Medical Genomics, Institute of Health Science, Shanghai Institute for Biological Sciences and Graduate School, Chinese Academy of Sciences, and Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai 200025, People's Republic of China.
authors.forename: Lin-Jia
authors.initials: LJ
authors.lastname: Jiang
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
authors.forename: Xian-Yang
authors.initials: XY
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Zhang
authors.forename: Wu
authors.initials: W
authors.lastname: Zhang
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.forename: Zhu-Gang
authors.initials: ZG
authors.lastname: Wang
authors.forename: Jun-Min
authors.initials: JM
authors.lastname: Li
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
mesh_terms: D049109:Cell Proliferation; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014212:Tretinoin; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases