Altered Regulation of ELAVL1/HuR in HLA-B27–Expressing U937 Monocytic Cells

Sahlberg, Anna S.; Ruuska, Marja; Granfors, Kaisa; Penttinen, Markus A.

doi:10.1371/journal.pone.0070377

Cited by 7 publications

(8 citation statements)

References 45 publications

(90 reference statements)

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“…Interestingly, enhanced Salmonella replication has been described within HLA-B27-transfected U937 monocytic cells, possibly mediated through effects of B27 heavy chains on the RNA-stabilizing protein Human antigen R (68).…”

Section: Hla-b27 the Unfolded Protein Response And The Endoplasmic Rmentioning

confidence: 99%

Hla-B27

Bowness

2015

Annu. Rev. Immunol.

220

169

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Possession of the human leukocyte antigen (HLA) class I molecule B27 is strongly associated with ankylosing spondylitis (AS), but the pathogenic role of HLA-B27 is unknown. Two broad theories most likely explain the role of HLA-B27 in AS pathogenesis. The first is based on the natural immunological function of HLA-B27 of presenting antigenic peptides to cytotoxic T cells. Thus, HLA-B27-restricted immune responses to self-antigens, or arthritogenic peptides, might drive immunopathology. B27 can also "behave badly," misfolding during assembly and leading to endoplasmic reticulum stress and autophagy responses. β2m-free B27 heavy chain structures including homodimers (B272) can also be expressed at the cell surface following endosomal recycling of cell surface heterotrimers. Cell surface free heavy chains and B272 bind to innate immune receptors on T, NK, and myeloid cells with proinflammatory effects. This review describes the natural function of HLA-B27, its disease associations, and the current theories as to its pathogenic role.

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Section: Hla-b27 the Unfolded Protein Response And The Endoplasmic Rmentioning

confidence: 99%

Hla-B27

Bowness

2015

Annu. Rev. Immunol.

220

169

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“…Alterations to the stability and translation efficiency of mRNAs result in the disruption of gene expression patterns ( 13 ). Human antigen R (HuR) is a human embryonic lethal abnormal vision-like (ELAV) RNA-binding protein, which belongs to the Hu family ( 14 ). In mammalian cells, HuR binds to AREs to adjust the instability of mRNAs ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-519 enhances HL60 human acute myeloid leukemia cell line proliferation by reducing the expression level of RNA-binding protein human antigen R

Huang

Dong

Wang

et al. 2015

Molecular Medicine Reports

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Previous studies have demonstrated that microRNAs (miRs) are involved in cell apoptosis. However, the role of miR-519 in acute myeloid leukemia (AML) has yet to be elucidated. The present study identified the effects of miR-519 on HL60 human acute myeloid leukemia cell growth and apoptosis. The expression levels of miR-519 were examined in AML cells, as well as AML tissue samples. Furthermore, cell viability and apoptosis were examined in HL60 cells transfected with miR-519 mimics, miR-519 inhibitors or a negative control. In addition, the effects of human antigen R (HuR) on cell apoptosis were investigated using specific small interfering RNA targeting HuR. The results demonstrated that the expression levels of miR-519 were significantly increased in the AML cells and the tissue samples, suggesting that miR-519 may contribute to abnormal HL60 cell proliferation. Upregulation of miR-519 expression decreased HL60 cell viability and induced cell apoptosis. Furthermore, knockdown of HuR reduced cell migration and enhanced cell apoptosis. The results of the present study indicate that miR-519 may contribute to HL60 cell apoptosis by regulating the expression of HuR.

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“…AREs are recognized by RNA binding proteins, which then affect gene expression by changing the stability and translation efficiency of mRNAs [6]. The human embryonic lethal abnormal vision-like (ELAV) protein HuR is an RNA binding protein in the Hu family [7]. It is widely expressed in mammalian cells and can bind to AREs to adjust mRNA stability.…”

Section: Introductionmentioning

confidence: 99%

MiR-291b-3p Induces Apoptosis in Liver Cell Line NCTC1469 by Reducing the Level of RNA-binding Protein HuR

Guo

Meng

et al. 2014

Cell Physiol Biochem

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Background: There is increasing evidence that miRNAs are involved in cellular apoptosis. However, the specific role of miR-291b-3p in apoptosis has not been elucidated. In the present study, we investigated the effect of miR-291b-3p on NCTC1469 cell growth and apoptosis. Methods: Cell viability and apoptosis were examined in NCTC1469 cells transfected with miR-291b-3p mimics, inhibitor miRNA or negative control. Using computational miRNA target prediction databases, HuR was predicted as a target of miR-291b-3p. Luciferase assay, immunofluorescence and western blot were used to further explore the effects of miR-291b-3p on HuR expression. In addition, the effect of HuR on cell apoptosis was evaluated using a HuR-specific siRNA. Results: TNF-α-induced hepatocyte apoptosis was accompanied by enhanced expression of miR-291b-3p, suggesting that miR-291b-3p might contribute to the apoptotic process. Follow-up experiments showed that upregulation of miR-291b-3p decreased cell viability and induced NCTC1469 cell apoptosis. Additionally, similar to the activity of miR-519, which is another member of the same miRNA family, miR-291b-3p suppressed HuR translation through binding to the HuR coding region (CR). We further showed that the downregulation of HuR expression by miR-291b-3p was accompanied by reduced Bcl-2 expression. Moreover, knockdown of HuR also impaired Bcl-2 expression and increased the ratio of Bax/Bcl-2. More significantly, downregulation of miR-291b-3p failed to increase Bcl2 expression in NCTC1469 cells that were co-transfected with siRNA-HuR. Finally, inhibition of miR-291b-3p led to reduced apoptosis, while knockdown of HuR by siRNA promoted apoptosis, even in NCTC1469 cells that were co-transfected with the miR-291b-3p inhibitor. Conclusion: The current data suggested that miR-291b-3p contributed to NCTC1469 cell apoptosis by regulating the expression of HuR, which in turn increased Bcl-2 stability.

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Altered Regulation of ELAVL1/HuR in HLA-B27–Expressing U937 Monocytic Cells

Cited by 7 publications

References 45 publications

Hla-B27

Hla-B27

MicroRNA-519 enhances HL60 human acute myeloid leukemia cell line proliferation by reducing the expression level of RNA-binding protein human antigen R

MiR-291b-3p Induces Apoptosis in Liver Cell Line NCTC1469 by Reducing the Level of RNA-binding Protein HuR

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