UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance

Saul, Meike J.; Stein, Stefan; Grez, Manuel; Jakobsson, Per‐Johan; Steinhilber, Dieter; Suess, Beatrix

doi:10.1038/srep31995

Cited by 19 publications

(27 citation statements)

References 46 publications

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“…For example, UPF1 regulates tumorigenesis by targeting Smad7 in hepatocellular carcinoma [21]. And UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance [35]. In this study, we found that UPF1 was also downregulated in gastric cancer.…”

Section: Discussionsupporting

confidence: 52%

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

Li¹,

Geng²,

Ren³

et al. 2017

Cell Physiol Biochem

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Background/Aims: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in numerous cancers. However, whether MALAT1 is regulated and the related mechanisms in gastric cancer remain unclear. Methods: Immunohistochemistry and qRT-PCR analyses were used to detect the expression levels of UPF1 and MALAT1 in gastric cancer and adjacent normal tissues. MTT, cell cycle, apoptosis and transwell assays were performed to examine the effects of UPF1 on cell cycle progression, cell proliferation, apoptosis, migration and invasion. Additionally, sodium bisulfate sequencing was used to test the promoter hypermethylation on UPF1 in gastric tumor tissues. Finally, RNA immunoprecipitation and luciferase reporter analyses demonstrated that UPF1 directly bound with MALAT1. Results: The expression of UPF1 was significantly downregulated in gastric cancer and negatively correlated with MALAT1 expression. Patients with lower expression of UPF1 had poorer prognosis than those with higher expression. Overexpression of UPF1 inhibited cell proliferation, cell cycle progression, cell migration and invasion, and promoted cell apoptosis in gastric cancer cells. Moreover, the UPF1-mediated inhibition of gastric cancer progression was reversed by overexpression of MALAT1. A profound downregulation of UPF1 in gastric tumor tissues was due to promoter hypermethylation. Overexpression of UPF1 increased nonsense-mediated mRNA decay (NMD) efficiency and thus led to downregulation of MALAT1. Conclusion: Our results demonstrate that UPF1 is a potential modulator of MALAT1 and that UPF1/MALAT1 pathway could be a therapeutic target for gastric cancer.

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Section: Discussionsupporting

confidence: 52%

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

Li¹,

Geng²,

Ren³

et al. 2017

Cell Physiol Biochem

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“…Previous studies proved that UPF.1 knockdown caused hnRNP-E2 overexpression. Hence, it will decrease the expression SI00A9 which also an important regulator for myeloid differentiation [30].…”

Section: Discussionmentioning

confidence: 99%

“…TRIB-2 could also induce the degradation of CEBPA protein. On the other hands, CEBPA protein interaction with AML1-ETO or c-jun was also known to inhibit the function of CEBPA itself [29][30][31][32][33]. It assumed that there are many factors that regulate the CEBPA expression and its activities in myeloid differentiation process.…”

Section: Discussionmentioning

confidence: 99%

HES-1 and CEBPA mRNA in Chronic and Late Phase (accelerated and blast crisis) of Chronic Myeloid Leukemia (CML) Patients

Rahmawati¹,

Fatmawati²,

Purwanto³

et al. 2017

J Leuk

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Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder of hematopoietic , characterized by Philadelphia chromosome containing BCR-ABL fusion gene. The gene encodes protein with constitutive tyrosine kinase activity result in myeloid proliferation and leads to form an early phase of CML called chronic phase. Unsuccessful treatment will lead to progression of the disease into late phase (accelerated and blast crisis). The mechanisms involving disease progression are still poorly understood. It is assumed that additional genetic event involves in differentiation blocking of myeloid progenitor cells, such as Hes-1 overexpression and CEBPA down regulation. However, study on the expression of these genes in CML patient's samples is still limited. This study aims to measure Hes-1 and CEBPA mRNA in chronic and late phase of CML patients. The peripheral blood mRNA level of Hes-1 was measured in CML patient's sample with BCR-ABL positive both in chronic phase (n=61) and late phase (n=17) using qRT-PCR with GAPDH as internal control. Hes-1 mRNA was statistically higher (p value=0.0) in the chronic phase (mean ± SD=97.8 ± 236.6) compared to those in late phase (mean ± SD=8.5 ± 30.7). In addition, even though CEBPA expression in chronic and late phase were not statistically different (p value=0.1), those in chronic phase (mean ± SD=5.2 ± 16.0) were generally higher compared to those in late phase (mean ± SD=1.7 ± 2.4). Hes-1 expression upregulated in 70.5% of chronic phase patients and in 17.6% of late phase patients, whereas CEBPA expression down regulated in 42.6% of chronic phase patients and in 47.1% in late phase patients. High standard deviation, particularly in mRNA Hes-1 gene expression measurement of the chronic phase, indicated the presence of individual variations in the sample that might be influenced by other genetic factors. This study found that Hes-1 mRNA is significantly higher in peripheral blood of chronic phase than blast crisis CML, whereas CEBPA mRNA is not different.

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“…This function is independent of the miR's seed region and operates exclusively by interference with a RBP. It was shown for the first time for miR-328 which acts as RNA decoy for the heterogeneous nuclear ribonucleoprotein E2 (hnRNP E2), a global gene expression repressor (Eiring et al, 2010;Saul et al, 2016Saul et al, , 2019b.…”

Section: Introductionmentioning

confidence: 99%

Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells

et al. 2020

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MicroRNAs (miRs) are one of the most important post-transcriptional repressors of gene expression. However, miR-574-5p has recently been shown to positively regulate the expression of microsomal prostaglandin E-synthase-1 (mPGES-1), a key enzyme in the prostaglandin E 2 (PGE 2 ) biosynthesis, by acting as decoy to the RNA-binding protein CUG-RNA binding protein 1 (CUGBP1) in human lung cancer. miR-574-5p exhibits oncogenic properties and promotes lung tumor growth in vivo via induction of mPGES-1-derived PGE 2 synthesis. In a mass spectrometry-based proteomics study, we now attempted to characterize this decoy mechanism in A549 lung cancer cells at a cellular level. Besides the identification of novel CUGBP1 targets, we identified that the interaction between miR-574-5p and CUGBP1 specifically regulates mPGES-1 expression. This is supported by the fact that CUGBP1 and miR-574-5p are located in the nucleus, where CUGBP1 regulates alternative splicing. Further, in a bioinformatical approach we showed that the decoy-dependent mPGES-1 splicing pattern is unique. The specificity of miR-574-5p/CUGBP1 regulation on mPGES-1 expression supports the therapeutic strategy of pharmacological inhibition of PGE 2 formation, which may provide significant therapeutic value for NSCLC patients with high miR-574-5p levels.

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UPF1 regulates myeloid cell functions and S100A9 expression by the hnRNP E2/miRNA-328 balance

Cited by 19 publications

References 46 publications

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

HES-1 and CEBPA mRNA in Chronic and Late Phase (accelerated and blast crisis) of Chronic Myeloid Leukemia (CML) Patients

Proteomics-Based Characterization of miR-574-5p Decoy to CUGBP1 Suggests Specificity for mPGES-1 Regulation in Human Lung Cancer Cells

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