Intact JAK–STAT signaling pathway is a prerequisite for STAT1 to reinforce the expression of RIG-G gene

Lou, Ye-jiang; Zhang, Zhanglin; Pan, Xiaorong; Xu, Gui-Ping; Jia, Pei-Min; Dong, Lei; Tong, Jianhua

doi:10.1016/j.yexcr.2010.10.025

Cited by 10 publications

(9 citation statements)

References 28 publications

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“…However, a potential contributing factor to the STAT1-dependence for ADAR1 induction seen in U3A cells may be the low level of STAT2 in U3A observed by us (Fig. 1B) and others (Lou et al, 2011). Other studies likewise have suggested a species-specific activity of STAT2.…”

Section: Discussionmentioning

confidence: 70%

STAT2-dependent induction of RNA adenosine deaminase ADAR1 by type I interferon differs between mouse and human cells in the requirement for STAT1

George

Samuel

2015

Virology

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Expression of adenosine deaminase acting on RNA1 (ADAR1) is driven by alternative promoters. Promoter PA, activated by interferon (IFN), produces transcripts that encode the inducible p150 ADAR1 protein, whereas PB specifies the constitutively expressed p110 protein. We show using Stat1−/−, Stat2−/− and IRF9−/− MEFs that induction of ADAR1 p150 occurs by STAT2- and IRF9-dependent signaling that is enhanced by, but not obligatorily dependent upon, STAT1. Chromatin immunoprecipitation analysis demonstrated STAT2 at the PA promoter in IFN-treated Stat1−/− cells, whereas IFN-treated wild-type cells showed both STAT1 and STAT2 bound at PA. By contrast, with human 2fTGH cells and mutants U3A or U6A, ADAR1 induction by IFN was dependent upon both STAT1 and STAT2. These results suggest that transcriptional activation of Adar1 by IFN occurs in the absence of STAT1 by a non-canonical STAT2-dependent pathway in mouse but not human cells.

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Section: Discussionmentioning

confidence: 70%

STAT2-dependent induction of RNA adenosine deaminase ADAR1 by type I interferon differs between mouse and human cells in the requirement for STAT1

George

Samuel

2015

Virology

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“…The Janus activated kinase/signal transducer and activator of transcription (JAK/STAT) pathway mediates ISG expression following interferon signaling [ 26 ]. Although alternate routes of IFIT3 induction, independent from STAT1 are known, STAT1 appears to be a key factor for enhanced IFIT3 expression [ 27 ]. The nuclear factor κB (NFκB) protein c-Rel has been shown to act as a regulator for the expression of several ISGs, including IFIT3 [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Overexpression of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in pancreatic cancer: cellular “pseudoinflammation” contributing to an aggressive phenotype

et al. 2014

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Inflammation contributes to important traits that cancer cells acquire during malignant progression. Gene array data recently identified upregulation of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in aggressive pancreatic cancer cells. IFIT3 belongs to the group of interferon stimulated genes (ISG), can be induced by several cellular stress stimuli and by its tetratricopeptide repeats interacts with a multitude of cellular proteins.Upregulation of IFIT3 was confirmed in the aggressive pancreatic cancer cell line L3.6pl compared with its less aggressive cell line of origin, COLO357FG. Transgenic induction of IFIT3 expression in COLO357FG resulted in greater mass of orthotopic tumors and higher prevalence of metastases. Several important traits that mediate malignancy were altered by IFIT3: increased VEGF and IL-6 secretion, chemoresistance and decreased starvation-induced apoptosis. IFIT3 showed binding to JNK and STAT1, the latter being an important inducer of IFIT3 expression. Despite still being alterable by “classical” IFN or NFκB signaling, our findings indicate constitutive - possibly auto-regulated - upregulation of IFIT3 in L3.6pl without presence of an adequate inflammatory stimulus. The transcription factor SOX9, which is linked to regulation of hypoxia-related genes, was identified as a key mediator of upregulation of the oncogene IFIT3 and thereby sustaining a “pseudoinflammatory” cellular condition.

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“…IRF-1 also induces Rig-G expression via an IRF-9/STAT2-dependent or IRF-9/STAT2-independent mechanism [ 21 ]. (3) STAT1 could significantly enhance the effects of the IRF-9/STAT2 complex or IRF-1 on Rig-G induction via an activated JAK-STAT pathway [ 22 ]. (4) The expression of PU.1 by ATRA directly binds to the promoter and increases the expression of Rig-G [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Rig-G is a growth inhibitory factor of lung cancer cells that suppresses STAT3 and NF-κB

Sun

Liu

et al. 2016

Oncotarget

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The expression of the retinoic acid-induced G (Rig-G) gene, an all trans retinoic acid (ATRA)-inducible gene, was observed in multiple cancer cells, including lung cancer cells. However, whether Rig-G is a tumor suppressor in lung cancer is unknown. Here, we found that ectopic expression of Rig-G can lead to a significant decrease in proliferation of lung cancer cells, resulting in an inhibition of tumor growth. Rig-G knockdown results in a modest increase in cell proliferation, as well as confers an increase in colony formation. Furthermore, transcriptome and pathway analyses of cancer cells revealed a fundamental impact of Rig-G on various growth signaling pathways, including the NF-κB pathway. Rig-G inhibits NF-κB activity by suppressing STAT3 in lung cancer cells. The downregulation of miR21 and miR181b-1 and subsequent activation of PTEN/Akt and CYLD/IκB signaling axis leading to decreased NF-κB activity required to maintain the tumor-inhibiting effect of Rig-G.. Our findings contribute to a better understanding of the antitumor effect mechanism of Rig-G, as well as offer a novel strategy for lung cancer therapy.

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Intact JAK–STAT signaling pathway is a prerequisite for STAT1 to reinforce the expression of RIG-G gene

Cited by 10 publications

References 28 publications

STAT2-dependent induction of RNA adenosine deaminase ADAR1 by type I interferon differs between mouse and human cells in the requirement for STAT1

STAT2-dependent induction of RNA adenosine deaminase ADAR1 by type I interferon differs between mouse and human cells in the requirement for STAT1

Overexpression of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in pancreatic cancer: cellular “pseudoinflammation” contributing to an aggressive phenotype

Rig-G is a growth inhibitory factor of lung cancer cells that suppresses STAT3 and NF-κB

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