Cold‐inducible RNA‐binding protein contributes to human antigen R and cyclin E1 deregulation in breast cancer

Guo, Xun; Wu, Yuehan; Hartley, Rebecca S.

doi:10.1002/mc.20582

Cited by 52 publications

(52 citation statements)

References 46 publications

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“…Gene ontology analysis indicated that all 5 transcripts were associated with stress responses (Table 2). None of these transcripts had been linked to CIRBP previously but the general association with stress responses is consistent with the proposed role of CIRBP in responding to cellular stress [15]–[17], [38]. The present work further supports this general concept.…”

Section: Discussionsupporting

confidence: 89%

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NF-κB-Dependent Role for Cold-Inducible RNA Binding Protein in Regulating Interleukin 1β

et al. 2013

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The cold inducible RNA binding protein (CIRBP) responds to a wide array of cellular stresses, including short wavelength ultraviolet light (UVC), at the transcriptional and post-translational level. CIRBP can bind the 3'untranslated region of specific transcripts to stabilize them and facilitate their transport to ribosomes for translation. Here we used RNA interference and oligonucleotide microarrays to identify potential downstream targets of CIRBP induced in response to UVC. Twenty eight transcripts were statistically increased in response to UVC and these exhibited a typical UVC response. Only 5 of the 28 UVC-induced transcripts exhibited a CIRBP-dependent pattern of expression. Surprisingly, 3 of the 5 transcripts (IL1B, IL8 and TNFAIP6) encoded proteins important in inflammation with IL-1β apparently contributing to IL8 and TNFAIP6 expression in an autocrine fashion. UVC-induced IL1B expression could be inhibited by pharmacological inhibition of NFκB suggesting that CIRBP was affecting NF-κB signaling as opposed to IL1B mRNA stability directly. Bacterial lipopolysaccharide (LPS) was used as an activator of NF-κB to further study the potential link between CIRBP and NFκB. Transfection of siRNAs against CIRBP reduced the extent of the LPS-induced phosphorylation of IκBα, NF-κB DNA binding activity and IL-1β expression. The present work firmly establishes a novel link between CIRBP and NF-κB signaling in response to agents with diverse modes of action. These results have potential implications for disease states associated with inflammation.

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Section: Discussionsupporting

confidence: 89%

“…We had anticipated that this strategy would lead to the identification of mRNAs bound directly by CIRBP [15]-[17], [38]. However, IL-1β is a key cytokine that modulates the expression of other secondary cytokines including IL-8 and TNFAIP6 [26], [27].…”

Section: Discussionmentioning

confidence: 99%

NF-κB-Dependent Role for Cold-Inducible RNA Binding Protein in Regulating Interleukin 1β

et al. 2013

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“…Cancer cells often further their survival and growth in hostile environments by increasing the expression of key SRFs such as CIRP, HSF1, HIF1, and NRF2 (45)(46)(47)(48). One of the consequences of SRF expression in hypoxic cancer cells is increased mutagenesis (29), similar to the SIM of TNRs observed here.…”

Section: Discussionsupporting

confidence: 56%

Environmental stress induces trinucleotide repeat mutagenesis in human cells

Chatterjee¹,

Lin²,

Santillan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication originlicensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.stress-induced mutagenesis | trinucleotide repeats | DNA rereplication | human cells | microsatellite repeats M icrosatellite repeats-runs of one to eight nucleotides repeated in tandem-account for 3% of the DNA in the human genome (1). These repeats are remarkably dynamic, mutating at rates several orders of magnitude higher than the rates of point mutations (2, 3). Microsatellite mutations typically change the number of repeated units in the tract, adding or removing individual units, making the mutations predictable and readily reversible, in contrast to point mutations. Growing evidence implicates microsatellite repeats as modifiers of gene function, traits, and diseases.

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“…In addition to transcriptional control, cyclin E1 mRNA stability is positively regulated in breast cancer cells by the RNA binding proteins HuR and CIRP [17, 27]. To ask if regulation of these proteins could also underlie changes in cyclin E1, we assessed their relative protein levels.…”

Section: Resultsmentioning

confidence: 99%

Three-dimensional collagen represses cyclin E1 via β1 integrin in invasive breast cancer cells

Guo

Brandt

et al. 2010

Breast Cancer Res Treat

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The behavior of breast epithelial cells is influenced by their microenvironment, which includes stromal cells and extracellular matrix (ECM). During cancer progression, the tissue microenvironment fails to control proliferation and differentiation, resulting in uncontrolled growth and invasion. Upon invasion, the ECM encountered by breast cancer cells changes from primarily laminin and collagen IV to primarily collagen I. We show here that culturing invasive breast cancer cells in 3-dimensional (3D) collagen I inhibits proliferation through direct regulation of cyclin E1, a G1/S regulator that is overexpressed in breast cancer. When the breast cancer cell line MDA-MB-231 was cultured within 3D collagen I gels, the G1/S transition was inhibited as compared to cells cultured on conventional 2D collagen or plastic dishes. Cells in 3D collagen downregulated cyclin E1 protein and mRNA, with no change in cyclin D1 level. Cyclin D1 was primarily cytoplasmic in 3D cultures and this was accompanied by decreased phosphorylation of Rb, a nuclear target for both cyclin E1- and cyclin D1-associated kinases. Positive regulators of cyclin E1 expression, the transcription factor c-Myc and cold-inducible RNA binding protein (CIRP), were decreased in 3D collagen cultures, while the collagen I receptor β1 integrin was greatly increased. Inhibition of β1 integrin function rescued proliferation and cyclin E1 expression as well as c-Myc expression and Rb phosphorylation, but cyclin D1 remained cytoplasmic. We conclude that cyclin E1 is repressed independent of effects on cyclin D1 in a 3-dimensional collagen environment and dependent on β1 integrin interaction with collagen I, reducing proliferation of invasive breast cancer cells.

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Cold‐inducible RNA‐binding protein contributes to human antigen R and cyclin E1 deregulation in breast cancer

Cited by 52 publications

References 46 publications

NF-κB-Dependent Role for Cold-Inducible RNA Binding Protein in Regulating Interleukin 1β

NF-κB-Dependent Role for Cold-Inducible RNA Binding Protein in Regulating Interleukin 1β

Environmental stress induces trinucleotide repeat mutagenesis in human cells

Three-dimensional collagen represses cyclin E1 via β1 integrin in invasive breast cancer cells

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