Swiprosin‐1: Its Expression and Diverse Biological Functions

Thylur, Ramesh P.; Gowda, Raghavendra; Mishra, Sumita; Jun, Chang Duk

doi:10.1002/jcb.26199

Cited by 18 publications

(15 citation statements)

References 50 publications

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“…High expression levels of ST13 are associated with reduced cell migration and proliferation of colorectal cancer cells (62). Swiprosin 1, which is involved in cortical cytoskeleton dynamics among other functions (63,64), was also decreased in the spleen after 48 h of kynurenine administration (ratio −1.14).…”

Section: Mass Spectroscopy; Prolonged (48 H) Groupmentioning

confidence: 99%

Quinolinate as a Marker for Kynurenine Metabolite Formation and the Unresolved Question of NAD+ Synthesis During Inflammation and Infection

et al. 2020

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Quinolinate (Quin) is a classic example of a biochemical double-edged sword, acting as both essential metabolite and potent neurotoxin. Quin is an important metabolite in the kynurenine pathway of tryptophan catabolism leading to the de novo synthesis of nicotinamide adenine dinucleotide (NAD + ). As a precursor for NAD + , Quin can direct a portion of tryptophan catabolism toward replenishing cellular NAD + levels in response to inflammation and infection. Intracellular Quin levels increase dramatically in response to immune stimulation [e.g., lipopolysaccharide (LPS) or pokeweed mitogen (PWM)] in macrophages, microglia, dendritic cells, and other cells of the immune system. NAD + serves numerous functions including energy production, the poly ADP ribose polymerization (PARP) reaction involved in DNA repair, and the activity of various enzymes such as the NAD + -dependent deacetylases known as sirtuins. We used highly specific antibodies to protein-coupled Quin to delineate cells that accumulate Quin as a key aspect of the response to immune stimulation and infection. Here, we describe Quin staining in the brain, spleen, and liver after LPS administration to the brain or systemic PWM administration. Quin expression was strong in immune cells in the periphery after both treatments, whereas very limited Quin expression was observed in the brain even after direct LPS injection. Immunoreactive cells exhibited diverse morphology ranging from foam cells to cells with membrane extensions related to cell motility. We also examined protein expression changes in the spleen after kynurenine administration. Acute (8 h) and prolonged (48 h) kynurenine administration led to significant changes in protein expression in the spleen, including multiple changes involved with cytoskeletal rearrangements associated with cell motility. Kynurenine administration resulted in several expression level changes in proteins associated with heat shock protein 90 (HSP90), a chaperone for the aryl-hydrocarbon receptor (AHR), which is the primary kynurenine Moffett et al.Quinolinate as Kynurenine Marker and NAD + Source metabolite receptor. We propose that cells with high levels of Quin are those that are currently releasing kynurenine pathway metabolites as well as accumulating Quin for sustained NAD + synthesis from tryptophan. Further, we propose that the kynurenine pathway may be linked to the regulation of cell motility in immune and cancer cells.

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Section: Mass Spectroscopy; Prolonged (48 H) Groupmentioning

confidence: 99%

Quinolinate as a Marker for Kynurenine Metabolite Formation and the Unresolved Question of NAD+ Synthesis During Inflammation and Infection

et al. 2020

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“…However, it promoted metastasis in B16F10 cells. 48 Taken together, these data suggested that STC2 promoted CRC progress by regulating a group of target genes.…”

Section: Discussionmentioning

confidence: 85%

Gene expression analyses identify a relationship between stanniocalcin 2 and the malignant behavior of colorectal cancer

Wang

Sahengbieke

et al. 2018

OTT

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BackgroundColorectal cancer (CRC) is one of the main causes of cancer-related death worldwide. Stanniocalcin 2 (STC2), a secreted glycoprotein, has been suggested to exert various functions in progression of many cancers. However, the precise biological role in CRC is not fully understood. Therefore, this study based on several public datasets aims at investigating the roles of STC2 in CRC.MethodsWe used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to evaluate the STC2 expression and its clinical significance in CRC. Cell migration and invasion by STC2 overexpression and knockdown were assessed using Transwell migration and Matrigel invasion assays. We next performed RNAseq analysis on SW480 cells with or without STC2 overexpression. Differentially expressed genes were selected by using fold-change >5 and P-value <0.05.ResultsIn this study, we found that STC2 level was significantly higher in CRC than that in adjacent noncancerous tissues from TCGA and GEO. Tumors with high mRNA levels of STC2 were more common in patients with rectal cancer, left-sided CRC, advanced T-stage (T3–T4), positive lymph node involvement and advanced AJCC-stage (III–IV) from TCGA. STC2 displayed the negative correlation with the expressions of epithelial cell markers, while it was positively correlated with the expressions of mesenchymal cell markers, MMPs and the epithelial-mesenchymal transition (EMT)-related transcriptional factors. Furthermore, we found that STC2 promoted cell migration and invasion in vitro. And a group of differentially expressed genes, which were modulated by STC2, were identified from RNAseq analyses.ConclusionOur study demonstrates that STC2 is overexpressed in CRC compared with normal tissues, and promotes CRC cell migration and invasion. Our data suggest that STC2 may be used as a potential biomarker for clinical application and target therapy in future.

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“…In total, 25 rare variants show allelic imbalance biased toward the deleterious alternative allele (20 splice and 5 stop-gain). Among those, one variant is in EFHD2, a gene coding for Ca 2+ adapter protein involved in B-cell apoptosis, NF-kB mediated inflammatory response, and immune cell activation and motility [30][31][32][33]. The carrier of this event was diagnosed with idiopathic cardiomyopathy, where accompanying symptoms (elevated inflammatory markers, Raynaud's disease, and alopecia) are indicative of auto-immune issues.…”

Section: Allele-specific Expression Outliers In Rare Disease Casesmentioning

confidence: 99%

Identification of rare-disease genes in diverse undiagnosed cases using whole blood transcriptome sequencing and large control cohorts

Frésard

Smail²,

et al. 2018

Preprint

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RNA sequencing (RNA-seq) is a complementary approach for Mendelian disease diagnosis for patients in whom exome-sequencing is not informative. For both rare neuromuscular and mitochondrial disorders, its application has improved diagnostic rates. However, the generalizability of this approach to diverse Mendelian diseases has yet to be evaluated. We sequenced whole blood RNA from 56 cases with undiagnosed rare diseases spanning 11 diverse disease categories to evaluate the general application of RNA-seq to Mendelian disease diagnosis. We developed a robust approach to compare rare disease cases to existing large sets of RNA-seq controls (N=1,594 external and N=31 family-based controls) and demonstrated the substantial impacts of gene and variant filtering strategies on disease gene identification when combined with RNA-seq. Across our cohort, we observed that RNA-seq yields a 8.5% diagnostic rate. These diagnoses included diseases where blood would not intuitively reflect evidence of disease. We identified RARS2 as an under-expression outlier containing compound heterozygous pathogenic variants for an individual exhibiting profound global developmental delay, seizures, microcephaly, hypotonia, and progressive scoliosis. We also identified a new splicing junction in KCTD7 for an individual with global developmental delay, loss of milestones, tremors and seizures. Our study provides a broad evaluation of blood RNA-seq for the diagnosis of rare disease.

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Swiprosin‐1: Its Expression and Diverse Biological Functions

Cited by 18 publications

References 50 publications

Quinolinate as a Marker for Kynurenine Metabolite Formation and the Unresolved Question of NAD+ Synthesis During Inflammation and Infection

Quinolinate as a Marker for Kynurenine Metabolite Formation and the Unresolved Question of NAD+ Synthesis During Inflammation and Infection

Gene expression analyses identify a relationship between stanniocalcin 2 and the malignant behavior of colorectal cancer

Identification of rare-disease genes in diverse undiagnosed cases using whole blood transcriptome sequencing and large control cohorts

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