A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma

Chen, Lih‐Chyang; Chen, Chia Chun; Li, Ying; Tsang, Ngan‐Ming; Chang, Yu‐Sun; Hsueh, Chuen

doi:10.1038/modpathol.2010.193

Cited by 61 publications

(64 citation statements)

References 38 publications

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“…6D). COMMD7 (You et al ., 2017), ITGA1 (Boudjadi et al ., 2013; Gulubova, 2004; Schadendorf et al ., 1996), RAB3D (Luo et al ., 2016; Yang et al ., 2003), and TNFAIP2 (Chen et al ., 2011; Jia et al ., 2016) have all been shown to be upregulated in various cancers including PDAC. While we cannot assume these changes will be universal in all PDAC samples, this consistency suggests that some of these genes could make promising targets or biomarkers for APE1‐based therapy or combination therapies that potentially will be useful across multiple PDAC tumor subtypes and in other tumor types.…”

Section: Discussionmentioning

confidence: 99%

APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing

et al. 2017

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Apurinic/apyrimidinic endonuclease 1/redox factor‐1 (APE1/Ref‐1 or APE1) is a multifunctional protein that regulates numerous transcription factors associated with cancer‐related pathways. Because APE1 is essential for cell viability, generation of APE1‐knockout cell lines and determining a comprehensive list of genes regulated by APE1 has not been possible. To circumvent this challenge, we utilized single‐cell RNA sequencing to identify differentially expressed genes (DEGs) in relation to APE1 protein levels within the cell. Using a straightforward yet novel statistical design, we identified 2837 genes whose expression is significantly changed following APE1 knockdown. Using this gene expression profile, we identified multiple new pathways not previously linked to APE1, including the EIF2 signaling and mechanistic target of Rapamycin pathways and a number of mitochondrial‐related pathways. We demonstrate that APE1 has an effect on modifying gene expression up to a threshold of APE1 expression, demonstrating that it is not necessary to completely knockout APE1 in cells to accurately study APE1 function. We validated the findings using a selection of the DEGs along with siRNA knockdown and qRT‐PCR. Testing additional patient‐derived pancreatic cancer cells reveals particular genes (ITGA1,TNFAIP2,COMMD7,RAB3D) that respond to APE1 knockdown similarly across all the cell lines. Furthermore, we verified that the redox function of APE1 was responsible for driving gene expression of mitochondrial genes such as PRDX5 and genes that are important for proliferation such as SIPA1 and RAB3D by treating with APE1 redox‐specific inhibitor, APX3330. Our study identifies several novel genes and pathways affected by APE1, as well as tumor subtype specificity. These findings will allow for hypothesis‐driven approaches to generate combination therapies using, for example, APE1 inhibitor APX3330 with other approved FDA drugs in an innovative manner for pancreatic and other cancer treatments.

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Section: Discussionmentioning

confidence: 99%

APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing

et al. 2017

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“…This finding is more in line with its involvement in invasion and metastasis. 44 We are aware of the limitations of this study, such as the samples size, but due to the high cost and labor associated with the RRBS methodology, the number of samples in the validation set enhances the credibility of the RRBS genome wide results. As the technology becomes more accessible and cheaper, we plan larger size studies.…”

Section: Discussionmentioning

confidence: 99%

DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia

et al. 2014

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“…Cell Culture-NPC TW02 and HK1 cells were cultured as previously described (32,33) and THP-1 cells were culture in Roswell Park Memorial Institute medium (33). Lentiviruses were established following the protocol of the RNAi Core of Taiwan (http://rnail.genmed.…”

Section: Methodsmentioning

confidence: 99%

Interactome-wide Analysis Identifies End-binding Protein 1 as a Crucial Component for the Speck-like Particle Formation of Activated Absence in Melanoma 2 (AIM2) Inflammasomes

Wang

Hsu

Chen

et al. 2012

Molecular & Cellular Proteomics

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Inflammasomes are cytoplasmic receptors that can recognize intracellular pathogens or danger signals and are critical for interleukin 1␤ production. Although several key components of inflammasome activation have been identified, there has not been a systematic analysis of the protein components found in the stimulated complex. In this study, we used the isobaric tags for relative and absolute quantification approach to systemically analyze the interactomes of the NLRP3, AIM2, and RIG-I inflammasomes in nasopharyngeal carcinoma cells treated with specific stimuli of these interactomes (H 2 O 2 , poly (dA:dT), and EBV noncoding RNA, respectively). We identified a number of proteins that appeared to be involved in the interactomes and also could be precipitated with antiapoptosis-associated speck-like protein containing caspase activation and recruitment domain antibodies after stimulation. Among them, end binding protein 1 was an interacting component in all three interactomes. Silencing of end binding protein 1 expression by small interfering RNA inhibited the activation of the three inflammasomes, as indicated by reduced levels of interleukin 1␤ secretion. We confirmed that end binding protein 1 directly interacted with AIM2 and ASC in vitro and in vivo. Most importantly, fluorescence confocal microscopy showed that end binding protein 1 was required for formation of the speck-like particles that represent activation of the AIM2 inflammasome. In nasopharyngeal carcinoma tissues, immunohistochemical staining showed that end binding protein 1 expression was elevated and significantly correlated with AIM2 and ASC expression in nasopharyngeal carcinoma tumor cells. In sum, we profiled the interactome components of three inflammasomes and show for the first time that end binding protein 1 is crucial for the speck-like particle formation that represents activated inflammasomes. Molecular & Cellular

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A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma

Cited by 61 publications

References 38 publications

APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing

APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing

DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia

Interactome-wide Analysis Identifies End-binding Protein 1 as a Crucial Component for the Speck-like Particle Formation of Activated Absence in Melanoma 2 (AIM2) Inflammasomes

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