High Cytoplasmic Expression of the Orphan Nuclear Receptor NR4A2 Predicts Poor Survival in Nasopharyngeal Carcinoma

Wang, Jian; Yang, Jing; Li, Binbin; He, Zhiwei

doi:10.7314/apjcp.2013.14.5.2805

Cited by 12 publications

(7 citation statements)

References 22 publications

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“…In the same study, PML expression was demonstrated to be negatively correlated with OPA1 expression that is needed for proper functioning of mitochondria under hyperglycemic conditions or doxorubicin treatment, implying an association between those two gene expressions 55 . On the other hand, ATF2 , SMAD2/3 , and NR4A2 have oncogenic potential, which is in line with our findings 56‐59 . However, further research is needed for all TFs mentioned earlier to better understand their involvement in HNSC carcinogenesis and their association with DHX36 , OPA1 , and SENP2 .…”

Section: Discussionsupporting

confidence: 86%

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Comprehensive in silico analysis for identification of novel candidate target genes, including DHX36, OPA1, and SENP2, located on chromosome 3q in head and neck cancers

et al. 2020

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Background: Major milestones of head and neck carcinogenesis have been associated with various genetic abnormalities; however, a clear picture of the molecular networks deregulated during the carcinogenesis of head and neck squamous cell carcinoma (HNSC) has not yet completely revealed. Methods: In this study, we used in silico tools and online data sets to evaluate the underlying reasons for the expressional changes of genes residing within the chromosome 3q and to help understanding their contributions to HNSC carcinogenesis. Results: We found that 13 of 20 most upregulated genes in HNSC are localized to 3q. Further analysis revealed a gene signature consisting of DHX36, OPA1, and SENP2, which showed significant correlation in HNSC samples and potentially be deregulated through similar mechanisms including DNA amplification, transcriptional, and posttranscriptional regulation. Conclusions: Considering our findings, we suggest DHX36, OPA1, and SENP2 genes as overexpressed in HNSC tumors and that might be concurrently involved in HNSC carcinogenesis, tumor progression, and induction of angiogenic pathways.

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Section: Discussionsupporting

confidence: 86%

“…55 On the other hand, ATF2, SMAD2/3, and NR4A2 have oncogenic potential, which is in line with our findings. [56][57][58][59] However, further research is needed for all TFs mentioned earlier to better understand their involvement in HNSC carcinogenesis and their association with DHX36, OPA1, and SENP2.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive in silico analysis for identification of novel candidate target genes, including DHX36, OPA1, and SENP2, located on chromosome 3q in head and neck cancers

et al. 2020

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“…Nurr1 is a potential novel marker for progression in human prostate cancer (24). High cytoplasmic expression of Nurr1 predicts poor survival in bladder cancer and nasopharyngeal carcinoma (11,25). Nurr1 is also a key target gene of thromboxane A2 receptors and is critical for the proliferation of lung carcinoma cells (26).…”

Section: Univariate Cox Regression Multivariate Cox Regression ------mentioning

confidence: 99%

Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

Chen

et al. 2016

Experimental and Therapeutic Medicine

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Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets.

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“…NR4A proteins, whose activities are context and tissue specific, localize both in the nucleus and in the cytoplasm. In the nucleus, they are reported to act as a transcription factors via binding to NBRE (NGF‐induced B factor‐response element) and related consensus sequences on DNA; in the cytoplasm, they have been shown to intersect different molecular pathways by protein–protein interactions, and increased cytosolic NR4A1 or NR4A2 protein levels have been associated with tumor aggressiveness . As EMC chimeras retain the DNA binding domain of NR4A3, they potentially recognize NBRE consensus sites .…”

Section: Introductionmentioning

confidence: 99%

NR4A3 fusion proteins trigger an axon guidance switch that marks the difference between EWSR1 and TAF15 translocated extraskeletal myxoid chondrosarcomas

Brenca

Stacchiotti

Fassetta

et al. 2019

The Journal of Pathology

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Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma histotype with uncertain differentiation. EMC is hallmarked by the rearrangement of the NR4A3 gene, which in most cases fuses with EWSR1 or TAF15. TAF15‐translocated EMC seem to feature a more aggressive course compared to EWSR1‐positive EMCs, but whether the type of NR4A3 chimera impinges upon EMC biology is still largely undefined. To gain insights on this issue, a series of EMC samples (7 EWSR1‐NR4A3 and 5 TAF15‐NR4A3) were transcriptionally profiled. Our study unveiled that the two EMC variants display a distinct transcriptional profile and that the axon guidance pathway is a major discriminant. In particular, class 4–6 semaphorins and axonal guidance cues endowed with pro‐tumorigenic activity were more expressed in TAF15‐NR4A3 tumors; vice versa, class 3 semaphorins, considered to convey growth inhibitory signals, were more abundant in EWSR1‐NR4A3 EMC. Intriguingly, the dichotomy in axon guidance signaling observed in the two tumor variants was recapitulated in in vitro cell models engineered to ectopically express EWSR1‐NR4A3 or TAF15‐NR4A3. Moreover, TAF15‐NR4A3 cells displayed a more pronounced tumorigenic potential, as assessed by anchorage‐independent growth. Overall, our results indicate that the type of NR4A3 chimera dictates an axon guidance switch and impacts on tumor cell biology. These findings may provide a framework for interpretation of the different clinical–pathological features of the two EMC variants and lay down the bases for the development of novel patient stratification criteria and therapeutic approaches. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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High Cytoplasmic Expression of the Orphan Nuclear Receptor NR4A2 Predicts Poor Survival in Nasopharyngeal Carcinoma

Cited by 12 publications

References 22 publications

Comprehensive in silico analysis for identification of novel candidate target genes, including DHX36, OPA1, and SENP2, located on chromosome 3q in head and neck cancers

Comprehensive in silico analysis for identification of novel candidate target genes, including DHX36, OPA1, and SENP2, located on chromosome 3q in head and neck cancers

Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

NR4A3 fusion proteins trigger an axon guidance switch that marks the difference between EWSR1 and TAF15 translocated extraskeletal myxoid chondrosarcomas

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