Death receptor 5 expression is inversely correlated with prostate cancer progression

Hernandez‐Cueto, Angeles; Hernández-Cueto, Daniel Dimitri; Antonio‐Andres, Gabriela; Mendoza‐Marin, Marisela; Jiménez-Gutiérrez, Carlos; Sandoval‐Mejia, Ana Lilia; Mora‐Campos, Rosario; González-Bonilla, César; Vega, Mario I.; Bonavida, Benjamin; Huerta-Yépez, Sara

doi:10.3892/mmr.2017.7234

Cited by 2 publications

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“…TNFRSF10B/DR5 delivers apoptotic signals to the cell and induces apoptosis in cancer cells [23]. The expression level of TNFRSF10B was associated with tumor progression and apoptosis [24]. Furthermore, the high expression of DR5 mediated the extrinsic apoptotic pathway in various cancer cells [25].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of necroptosis-related prognostic gene signature and tumor immune microenvironment infiltration characterization in esophageal carcinoma

et al. 2022

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Background Esophageal carcinoma (ESCA) is a common malignancy with a poor prognosis. Previous research has suggested that necroptosis is involved in anti-tumor immunity and promotes oncogenesis and cancer metastasis, which in turn affects tumor prognosis. However, the role of necroptosis in ESCA is unclear. This study aimed to investigate the relationships between necroptosis-related genes (NRGs) and ESCA. Methods and results The clinical data and gene expression profiles of ESCA patients were extracted from The Cancer Genome Atlas (TCGA), and 159 NRGs were screened from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We then identified 52 differentially expressed NRGs associated with ESCA and used them for further analysis. Gene ontology (GO) and KEGG functional enrichment analyses showed that these NRGs were mostly associated with the regulation of necroptosis, Influenza A, apoptosis, NOD-like receptor, and NF-Kappa B signaling pathway. Next, univariate and multivariate Cox regression and LASSO analysis were used to identify the correlation between NRGs and the prognosis of ESCA. We constructed a prognostic model to predict the prognosis of ESCA based on SLC25A5, PPIA, and TNFRSF10B; the model classified patients into high- and low-risk subgroups based on the patient’s risk score. Furthermore, the receiver operating characteristic (ROC) curve was plotted, and the model was affirmed to perform moderately well for prognostic predictions. In addition, Gene Expression Omnibus (GEO) datasets were selected to validate the applicability and prognostic value of our predictive model. Based on different clinical variables, we compared the risk scores between the subgroups of different clinical features. We also analyzed the predictive value of this model for drug sensitivity. Moreover, Immunohistochemical (IHC) validation experiments explored that these three NRGs were expressed significantly higher in ESCA tissues than in adjacent non-tumor tissues. In addition, a significant correlation was observed between the three NRGs and immune-cell infiltration and immune checkpoints in ESCA. Conclusions In summary, we successfully constructed and validated a novel necroptosis-related signature containing three genes (SLC25A5, PPIA, and TNFRSF10B) for predicting prognosis in patients with ESCA; these three genes might also play a crucial role in the progression and immune microenvironment of ESCA.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of necroptosis-related prognostic gene signature and tumor immune microenvironment infiltration characterization in esophageal carcinoma

et al. 2022

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“…Tissue microarray (TMA) blocks covering 21 randomly selected CRC and 6 controls from adjacent morphologically normal tissue were cut into 4‐mm sections and arrayed according to the Microarray technique with a semiautomatic ATA‐100 Chemicon system (Chemicon's Advanced Tissue Array) . TMAs were processed for IHC as previously described, using as primary antibodies anti‐YY1 (1/500), anti‐Fas (1/250) or normal IgG serum (negative control) (all from Santa Cruz Biotechnology, Santa Cruz, CA).…”

Section: Methodsmentioning

confidence: 99%

CRHR2/Ucn2 signaling is a novel regulator of miR‐7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas‐mediated apoptosis

Pothoulakis

Torre-Rojas

Durán-Padilla

et al. 2017

Intl Journal of Cancer

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Colorectal cancer (CRC) responds poorly to immuno-mediated cytotoxicity. Underexpression of corticotropin-releasing-hormone-receptor-2 (CRHR2) in CRC, promotes tumor survival, growth and Epithelial to Mesenchymal Transition (EMT), in vitro and in vivo. We explored the role of CRHR2 downregulation in CRC cell resistance to Fas/FasL-mediated apoptosis and the underlying molecular mechanism. CRC cell sensitivity to CH11-induced apoptosis was compared between Urocortin-2 (Ucn2)-stimulated parental and CRHR2-overexpressing CRC cell lines and targets of CRHR2/Ucn2 signaling were identified through in vitro and ex vivo analyses. Induced CRHR2/Ucn2 signaling in SW620 and DLD1 cells increased specifically their sensitivity to CH11-mediated apoptosis, via Fas mRNA and protein upregulation. CRC compared to control tissues had reduced Fas expression that was associated with lost CRHR2 mRNA, poor tumor differentiation and high risk for distant metastasis. YY1 silencing increased Fas promoter activity in SW620 and re-sensitized them to CH11-apoptosis, thus suggesting YY1 as a putative transcriptional repressor of Fas in CRC. An inverse correlation between Fas and YY1 expression was confirmed in CRC tissue arrays, while elevated YY1 mRNA was clinically relevant with advanced CRC grade and higher risk for distant metastasis. CRHR2/Ucn2 signaling downregulated specifically YY1 expression through miR-7 elevation, while miR-7 modulation in miR-7 SW620-CRHR2+ and miR-7 HCT116 cells, had opposite effects on YY1 and Fas expressions and cell sensitivity to CH11-killing. CRHR2/Ucn2 signaling is a negative regulator of CRC cell resistance to Fas/FasL-apoptosis via targeting the miR-7/YY1/Fas circuitry. CRHR2 restoration might prove effective in managing CRC response to immune-mediated apoptotic stimuli.

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Death receptor 5 expression is inversely correlated with prostate cancer progression

Cited by 2 publications

References 0 publications

Identification and validation of necroptosis-related prognostic gene signature and tumor immune microenvironment infiltration characterization in esophageal carcinoma

Identification and validation of necroptosis-related prognostic gene signature and tumor immune microenvironment infiltration characterization in esophageal carcinoma

CRHR2/Ucn2 signaling is a novel regulator of miR‐7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas‐mediated apoptosis

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