Expression of Dual-Specificity Phosphatase 5 Pseudogene 1 (DUSP5P1) in Tumor Cells

Staege, Martin S.; Müller, Katja; Kewitz, Stefanie; Volkmer, Ines; Mauz‐Körholz, Christine; Bernig, Toralf; Körholz, Dieter

doi:10.1371/journal.pone.0089577

Cited by 19 publications

(17 citation statements)

References 62 publications

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“…At 3 months, we identified two regions on chromosome 1 associated with decreased methylation of the DUSP5P1 pseudogene in the family of MAPK phosphatases. Studies suggest that this gene may act as a tumor suppressor in hematopoietic malignancies [45,46]. In the current study, we observed a decrease in methylation following the MBC2 intervention, which may indicate an upregulation of DUSP5P1 and tumor suppression.…”

Section: Discussionsupporting

confidence: 65%

Impact of a diet and activity health promotion intervention on regional patterns of DNA methylation

et al. 2019

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Background: Studies demonstrate the impact of diet and physical activity on epigenetic biomarkers, specifically DNA methylation. However, no intervention studies have examined the combined impact of dietary and activity changes on the blood epigenome. The objective of this study was to examine the impact of the Make Better Choices 2 (MBC2) healthy diet and activity intervention on patterns of epigenome-wide DNA methylation. The MBC2 study was a 9-month randomized controlled trial among adults aged 18-65 with non-optimal levels of health behaviors. The study compared three 12-week interventions to (1) simultaneously increase exercise and fruit/ vegetable intake, while decreasing sedentary leisure screen time; (2) sequentially increase fruit/vegetable intake and decrease leisure screen time first, then increase exercise; (3) increase sleep and decrease stress (control). We collected blood samples at baseline, 3 and 9 months, and measured DNA methylation using the Illumina EPIC (850 k) BeadChip. We examined region-based differential methylation patterns using linear regression models with the false discovery rate of 0.05. We also conducted pathway analysis using gene ontology (GO), KEGG, and IPA canonical pathway databases. Results: We found no differences between the MBC2 population (n = 340) and the subsample with DNA methylation measured (n = 68) on baseline characteristics or the impact of the intervention on behavior change. We identified no differentially methylated regions at baseline between the control versus intervention groups. At 3 versus 9 months, we identified 154 and 298 differentially methylated regions, respectively, between controls compared to pooled samples from sequential and simultaneous groups. In the GO database, we identified two gene ontology terms related to hemophilic cell adhesion and cell-cell adhesion. In IPA analysis, we found pathways related to carcinogenesis including PI3K/AKT, Wnt/β-catenin, sonic hedgehog, and p53 signaling. We observed an overlap between 3 and 9 months, including the GDP-L-fucose biosynthesis I, methylmalonyl metabolism, and estrogen-mediated cell cycle regulation pathways. Conclusions: The results demonstrate that the MBC2 diet and physical activity intervention impacts patterns of DNA methylation in gene regions related to cell cycle regulation and carcinogenesis. Future studies will examine DNA methylation as a biomarker to identify populations that may particularly benefit from incorporating health behavior change into plans for precision prevention.

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Section: Discussionsupporting

confidence: 65%

Impact of a diet and activity health promotion intervention on regional patterns of DNA methylation

et al. 2019

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“…HL is a lympho-proliferative disease with known re-activation of HERV-like sequences (Lamprecht et al, 2010 ; Staege et al, 2014 ). The majority of HL patients can be cured today, but the toxicity of the used therapy regimes is high.…”

Section: Resultsmentioning

confidence: 99%

WebHERV: A Web Server for the Computational Investigation of Gene Expression Associated With Endogenous Retrovirus-Like Sequences

et al. 2018

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More than eight percent of the human genome consists of human endogenous retroviruses (HERVs). Typically, the expression of HERVs is repressed, but varying activities of HERVs have been observed in diseases ranging from cancer to neuro-degeneration. Such activities can include the transcription of HERV-derived open reading frames, which can be translated into proteins. However, as a consequence of mutations that disrupt open reading frames, most HERV-like sequences have lost their protein-coding capacity. Nevertheless, these loci can still influence the expression of adjacent genes and, hence, mediate biological effects. Here, we present WebHERV (http://calypso.informatik.uni-halle.de/WebHERV/), a web server that enables the computational prediction of active HERV-like sequences in the human genome based on a comparison of genome coordinates of expressed sequences uploaded by the user and genome coordinates of HERV-like sequences stored in the specialized key-value store DRUMS. Using WebHERV, we predicted putative candidates of active HERV-like sequences in Hodgkin lymphoma (HL) cell lines, validated one of them by a modified SMART (switching mechanism at 5′ end of RNA template) technique, and identified a new alternative transcription start site for cytochrome P450, family 4, subfamily Z, polypeptide 1 (CYP4Z1).

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“…As an lncRNA, DUSP5P1 is a pseudogene of DUSP5. The DUSP5/ DUSP5P1 system could be responsible for regulation of BCL2L11 leading to the inhibition of apoptosis in HL cells (18). High expression of DUSP5P1 is identified in high-risk AML patients and is associated with poor prognosis in AML (14).…”

Section: Discussionmentioning

confidence: 99%

C8orf76 Promotes Gastric Tumorigenicity and Metastasis by Directly Inducing lncRNA DUSP5P1 and Associates with Patient Outcomes

Wang

Liang

Zhang

et al. 2019

Clinical Cancer Research

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Purpose: We identified for the first time that C8orf76 (chromosome 8 open reading frame 76) is preferentially amplified in gastric cancer. We elucidated its role and clinical significance in gastric carcinogenesis. Experimental Design: The clinical impact of C8orf76 was assessed in 592 patients with gastric cancer. The biological function of C8orf76 was studied in vitro, in vivo, and in gastric cancer patient-derived organoid models. C8orf76 downstream effector and pathways were identified by RNA sequencing, chromatin immunoprecipitation sequencing, luciferase reporter, and electrophoretic mobility shift assay. Results: C8orf76 was upregulated in 69.74% and 65.71% of two independent cohorts of gastric cancers and was positively associated with C8orf76 amplification. Multivariate analysis showed that gastric cancer patients with C8orf76 amplification (cohort I, n ¼ 129; cohort II, n ¼ 107) or overexpression (n ¼ 356) had a significantly shortened survival. C8orf76 significantly promoted gastric cancer cell proliferation, cell-cycle transformation, and migration/invasion, but suppressed cell apoptosis. Silencing C8orf76 expression exerted opposite effects in vitro and significantly inhibited xenograft tumor growth, lung metastasis, and liver metastasis in nude mice. Silencing C8orf76 also significantly suppressed the growth of patient-derived organoids. Mechanically, C8orf76 activated MAPK/ERK signaling cascade. C8orf76 directly bound to the promoter region of lncRNA dual specificity phosphatase 5 pseudogene 1 (DUSP5P1) with a binding motif of AGGCTG and activated DUSP5P1 transcription. DUSP5P1 induced MAPK/ERK signaling and promoted gastric tumorigenesis. Knockdown DUSP5P1 abrogated the effect of C8orf76 in activating MAPK/ERK cascade and the tumor-promoting function. Conclusions: C8orf76 directly binds to oncogenic lncRNA DUSP5P1 to induce its expression and activates MAPK signaling. C8orf76 plays a pivotal oncogenic role in gastric carcinogenesis and is an independent prognostic factor for gastric cancer patients.

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Expression of Dual-Specificity Phosphatase 5 Pseudogene 1 (DUSP5P1) in Tumor Cells

Cited by 19 publications

References 62 publications

Impact of a diet and activity health promotion intervention on regional patterns of DNA methylation

Impact of a diet and activity health promotion intervention on regional patterns of DNA methylation

WebHERV: A Web Server for the Computational Investigation of Gene Expression Associated With Endogenous Retrovirus-Like Sequences

C8orf76 Promotes Gastric Tumorigenicity and Metastasis by Directly Inducing lncRNA DUSP5P1 and Associates with Patient Outcomes

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