Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

Gubin, Matthew M.; Calaluce, Robert; Davis, J. Wade; Magee, Joseph; Strouse, Connie S.; Shaw, Daniel P.; Ma, Lixin; Brown, Ashley N.; Hoffman, Timothy J.; Rold, Tammy L.; Atasoy, Ulus

doi:10.4161/cc.9.16.12711

Cited by 54 publications

(55 citation statements)

References 50 publications

(59 reference statements)

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“…Ectopic expression of CRABP2 markedly suppressed proliferation. In agreement with previous reports that HuR displays antiproliferative activities (27,(35)(36)(37), decreasing the expression level of this protein enhanced cell growth. Surprisingly, however, despite the presence of RA, decreasing the expression of HuR negated the ability of CRABP2 to inhibit cell growth.…”

Section: Crabp2 Inhibits Mammary Carcinoma Cell Growth By Two Distinctsupporting

confidence: 81%

Cellular Retinoic Acid-binding Protein 2 Inhibits Tumor Growth by Two Distinct Mechanisms

Vreeland

Levi

Zhang

et al. 2014

Journal of Biological Chemistry

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Background: CRABP2 delivers RA to its cognate nuclear receptor RAR and regulates gene expression by cooperating with HuR in stabilizing mRNAs. Results: In conjunction with HuR, CRABP2 regulates the expression of multiple cancer-related genes and suppresses tumor growth. Conclusion:The anticarcinogenic activities of CRABP2 are mediated by both HuR and RAR.Significance: The data demonstrate a novel mechanism through which CRABP2 inhibits tumorigenesis.

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Section: Crabp2 Inhibits Mammary Carcinoma Cell Growth By Two Distinctsupporting

confidence: 81%

Cellular Retinoic Acid-binding Protein 2 Inhibits Tumor Growth by Two Distinct Mechanisms

Vreeland

Levi

Zhang

et al. 2014

Journal of Biological Chemistry

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“…Additionally, the data obtained with our conditional knockout mouse model suggest that HuR-dependent and -independent control mechanisms of GATA-3 and Th2 cytokines may coexist. Consistent with this idea, we have recently demonstrated that HuR can positively or negatively control expression of the same genes in breast cancer cells depending on the cellular milieu (59,60).…”

Section: Discussionsupporting

confidence: 57%

Conditional Knockout of the RNA-Binding Protein HuR in CD4+ T Cells Reveals a Gene Dosage Effect on Cytokine Production

Gubin

Techasintana

Magee

et al. 2014

Mol Med

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The posttranscriptional mechanisms by which RNA binding proteins (RBPs) regulate T-cell differentiation and cytokine production in vivo remain unclear. The RBP HuR binds to labile mRNAs, usually leading to increases in mRNA stability and/or translation. Previous work demonstrated that HuR binds to the mRNAs encoding the Th2 transcription factor trans-acting T-cell-specific transcription factor (GATA-3) and Th2 cytokines interleukin (IL)-4 and IL-13, thereby regulating their expression. By using a novel conditional HuR knockout (KO)

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“…HuR performs its functions closely related with its translocation from the nucleus into cytoplasm by modulating mRNA stability and translation. The function of HuR has been reported in regulating gene expression in many cellular processes, such as cell-cycle control, tumorigenesis, inflammation, apoptosis, and cell stress response (40)(41)(42)(43)(44). We previously reported that the rapid decay of mRNA in activated T cells could be changed by the activation of HuR, which binds IL-13 mRNA 39 UTR in Th2 cells (24 We computationally detected two hits of the putative HuR signature motif in IL-17 mRNA 39 UTR, suggesting that IL-17 mRNA might be a direct target of HuR.…”

Section: Discussionmentioning

confidence: 99%

Posttranscriptional Gene Regulation of IL-17 by the RNA-Binding Protein HuR Is Required for Initiation of Experimental Autoimmune Encephalomyelitis

Chen

Cascio

Magee

et al. 2013

The Journal of Immunology

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IL-17 is a proinflammatory cytokine produced by activated Th17 cells and other immune cells. IL-17–producing Th17 cells are major contributors to chronic inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Although the transcriptional regulation of Th17 cells is well understood, the posttranscriptional regulation of IL-17 gene expression remains unknown. The RNA-binding protein HuR positively regulates the stability of many target mRNAs via binding the AU-rich elements present in the 3′ untranslated region of many inflammatory cytokines including IL-4, IL-13, and TNF-α. However, the regulation of IL-17 expression by HuR has not been established. CD4+ Th17 cells from HuR knockout mice had decreased IL-17 steady-state mRNA and protein levels compared with wild-type Th17 cells, as well as decreases in frequency of IL-17+ cells. Moreover, we demonstrated that HuR directly binds to the IL-17 mRNA 3′ untranslated region by using RNA immunoprecipitation and biotin pulldown assays. In addition, the knockout of HuR decreased cellular proliferation of CD4+ T cells. Mice with adoptively transferred HuR KO Th17 cells had delayed initiation and reduced disease severity in the onset of experimental autoimmune encephalomyelitis compared with wild-type Th17 cells. Our results reveal a HuR-induced posttranscriptional regulatory mechanism of Th17 differentiation that influences IL-17 expression. These findings may provide novel therapeutic targets for the treatment of Th17-mediated autoimmune neuroinflammation.

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Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

Cited by 54 publications

References 50 publications

Cellular Retinoic Acid-binding Protein 2 Inhibits Tumor Growth by Two Distinct Mechanisms

Cellular Retinoic Acid-binding Protein 2 Inhibits Tumor Growth by Two Distinct Mechanisms

Conditional Knockout of the RNA-Binding Protein HuR in CD4+ T Cells Reveals a Gene Dosage Effect on Cytokine Production

Posttranscriptional Gene Regulation of IL-17 by the RNA-Binding Protein HuR Is Required for Initiation of Experimental Autoimmune Encephalomyelitis

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