Epigenetic alterations of <i>gastrokine</i> 1 gene expression in gastric cancer

Altieri, Filomena; Stadio, Chiara Stella Di; Federico, Antonella; Miselli, Giuseppina; Palma, Maurizio De; Rippa, Emilia; Arcari, Paolo

doi:10.18632/oncotarget.14817

Cited by 21 publications

(25 citation statements)

References 44 publications

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“…We also identified a downstream target of KRAS (MUC16) as DEG, supporting KRAS implications in survival 33 . Also, we observed modifications of GKN1, KRT6, and ANKRD43 gene expressions in LTS, known to induce apoptosis and metastasis cancer 34,35 . A previous study showed REG4 as a serological marker for PDAC 36 .…”

Section: Discussionmentioning

confidence: 71%

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Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

Bhardwaj

Josse

Daele

et al. 2020

Preprint

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Background: Pancreatic ductal adenocarcinoma (PDAC) is categorized as the seventh leading cause of cancer mortality worldwide. Its predictive markers for long-term survival are not well known. Therefore, it is interesting to delineate individual-specific perturbed genes when comparing long-term (LT) and short-term (ST) PDAC survivors, and to exploit the integrative individual-and group-based transcriptome profiling.Method: Using a discovery cohort of 19 PDAC patients from CHU-Liège (Belgium), we first performed differential gene expression (DGE) analysis comparing LT to ST survivor. Second, we adopted unsupervised systems biology approaches to obtain gene modules linked to clinical features. Third, we created individual-specific perturbation profiles and identified key regulators across the LT patients. Furthermore, we applied two gene prioritization approaches: random walk-based Degree-Aware disease gene prioritizing (DADA) method to develop PDAC disease modules; Network-based Integration of Multi-omics Data (NetICS) to integrate group-based and individual-specific perturbed genes in relation to PDAC LT survival. Findings: We identified 173 differentially expressed genes (DEGs) in ST and LT survivors and five modules (including 38 DEGs) showing associations to clinical traits such as tumor size and chemotherapy. DGE analysis identified differences in genes involved in metabolic and cell cycle activity. Validation of DEGs in the molecular lab suggested a role of REG4 and TSPAN8 in PDAC survival. Individual-specific omics changes across LT survivors revealed biological signatures such as focal adhesion and extracellular matrix receptors, implying a potential role in molecular-level heterogeneity of LT PDAC survivors. Via NetICS and DADA we not only identified various known oncogenes such as CUL1, SCF62, EGF, FOSL1, MMP9, and TGFB1, but also highlighted novel genes (TAC1, KCNH7, IRS4, DKK4). Interpretation: Our proposed analytic workflow shows the advantages of combining clinical and omics data as well as individual-and group-level transcriptome profiling. It suggested novel potential transcriptome marks of LT survival heterogeneity in PDAC. Funding: Télévie-FRS-FNRS

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Section: Discussionmentioning

confidence: 71%

“…To analyses the effect of perturbed genes in PEEPs (gene is significantly perturbed or not) in LT survivor's heterogeneity, two-way clustering (biclustering) highlighted 64 gene clusters (appendix pp [33][34]. The largest cluster (cluster 15) consisted of 363 genes.…”

Section: Biclustering Of Functional Profilesmentioning

confidence: 99%

Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

Bhardwaj

Josse

Daele

et al. 2020

Preprint

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“…As already reported [7], for the Chip assay it was identified a 600 bp GKN1 promoter region that was divided into three segments of about 160 bp (A, B, and C). Compared with non-tumoral tissues, ChIP assays performed on these segments did not reveal a significant association of RUNX3 in tumoral tissues.…”

Section: Gkn1 Down-regulation In Gc Is Not Associated With Runx3 On Tmentioning

confidence: 70%

“…In fact, chromatin immunoprecipitation assays for the trimethylation of histone 3 at lysine 9 (H3K9triMe) and its specific histone-lysine N-methyltransferase (SUV39H1), performed on human specimens of normal and cancerous gastric tissues, showed that GKN1 down-regulation in GC tissues was associated with high levels of H3K9triMe and with the recruitment of SUV39H1 to the GKN1 promoter. These findings suggested that an epigenetic transcriptional complex could negatively regulate GKN1 expression in gastric tumors [7].…”

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confidence: 89%

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Down-Regulation of GKN1 in Gastric Cancer Is Not Associated with the RUNX3 Expression

Stadio¹,

Altieri²,

Federico³

et al. 2017

JBM

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Gastrokine 1 (GKN1) is a gastric mucosal protein highly expressed and secreted in normal individuals but during Helicobacter pylori infection or in gastric carcinogenesis it is strongly down-regulated or totally absent. In gastric cancer, the GKN1 gene is silenced through an epigenetic mechanism most likely mediated by a transcription factor that promotes on GKN1 promoter the activity of the enzymes SUV39H1 and HDACs. Because RUNX3 is a potential candidate in the regulation of molecular carcinogenesis process of stomach cancers, we tried to assess if RUNX3 could be involved in GKN1 down-regulation in GC. 17 paired of non-tumoral and tumoral surgical specimens from patients with gastric cancer were analyzed for GKN1 and RUNX3 by Western blotting and chromatin immunoprecipitation (Chip) assays. The overall results indicated that RUNX3 expression was not associated with the down-regulation of GKN1. The expression levels of RUNX3 in non-tumoral and tumoral samples suggest that RUNX3 does not act as a tumor suppressor but that it might play a complex oncogenic role in gastric cancer cells.

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miR‐34a Targets HDAC1‐Regulated H3K9 Acetylation on Lipid Accumulation Induced by Homocysteine in Foam Cells

Zhao

et al. 2017

J of Cellular Biochemistry

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Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation of miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated the effects of homocysteine (Hcy) on the expression of histone deacetylase 1 (HDAC1) and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased HDAC1 expression, which is regulated by miR-34a. The expression of HDAC1 increased and acetylation of histone H3 at lysine 9 (H3K9ac) decreased in the aorta of ApoE mice fed with high methionine diet, whereas miR-34a expression was inhibited. Over-expression of HDAC1 inhibited H3K9ac level and promoted the accumulation of total cholesterol, free cholesterol, and triglycerides in the foam cells. Furthermore, up-regulation of miR-34a reduced HDAC1 expression and inhibited the accumulation of total cholesterol (TC), free cholesterol (FC), and triglycerides (TG) in the foam cells. These data suggest that HDAC1-related H3K9ac plays a key role in Hcy-mediated lipid metabolism disorders, and that miR-34a may be a novel therapeutic target in Hcy-related atherosclerosis. J. Cell. Biochem. 118: 4617-4627, 2017. © 2017 Wiley Periodicals, Inc.

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Epigenetic alterations of gastrokine 1 gene expression in gastric cancer

Cited by 21 publications

References 44 publications

Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

Down-Regulation of GKN1 in Gastric Cancer Is Not Associated with the RUNX3 Expression

miR‐34a Targets HDAC1‐Regulated H3K9 Acetylation on Lipid Accumulation Induced by Homocysteine in Foam Cells

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