A Pan-Cancer Analysis of the Role of Selenoprotein P mRNA in Tumorigenesis

Yang, Yanni; Li, Daning; Wu, Wentao; Huang, Dingxing; Zheng, Haishi; Aihaiti, Yirixiati

doi:10.2147/ijgm.s332031

Cited by 8 publications

(9 citation statements)

References 54 publications

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“…The ubiquitous loss of mitochondrial thioredoxin reductase (TrxR2) in mice was associated with embryonic death at embryonic day 13 and the presentation of smaller embryos that were severely anemic with increased apoptosis in the liver [ 50 ]. A pan-cancer expression analysis revealed the association of selenoprotein P ( SELENOP ) with a better prognosis in most cancers, but a poorer prognosis in brain glioma and uterine corpus endometrioid carcinoma [ 51 ]. Furthermore, the overexpression of Glutathione peroxidases (GPXs) in AML patients compared to normal controls was significantly associated with a poor prognosis of overall survival [ 52 ].…”

Section: Regulation Of Signaling Pathways By Selenium In Cancermentioning

confidence: 99%

Therapeutic Benefits of Selenium in Hematological Malignancies

Ehudin

Golla

Trivedi

et al. 2022

IJMS

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Supplementing chemotherapy and radiotherapy with selenium has been shown to have benefits against various cancers. This approach has also been shown to alleviate the side effects associated with standard cancer therapies and improve the quality of life in patients. In addition, selenium levels in patients have been correlated with various cancers and have served as a diagnostic marker to track the efficiency of treatments or to determine whether these selenium levels cause or are a result of the disease. This concise review presents a survey of the selenium-based literature, with a focus on hematological malignancies, to demonstrate the significant impact of selenium in different cancers. The anti-cancer mechanisms and signaling pathways regulated by selenium, which impart its efficacious properties, are discussed. An outlook into the relationship between selenium and cancer is highlighted to guide future cancer therapy development.

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Section: Regulation Of Signaling Pathways By Selenium In Cancermentioning

confidence: 99%

Therapeutic Benefits of Selenium in Hematological Malignancies

Ehudin

Golla

Trivedi

et al. 2022

IJMS

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“…These downregulated genes ( P < 0.00001) overlapped with genes previously identified in control veins (Figure 4C) and also included the antiapoptotic regulator secreted frizzled-related protein 1 ( SFRP1 ), 41 the negative regulator of angiogenesis multimerin-2 ( MMRN2 ), 42 and negative regulator of vascular EC proliferation ( SELENOP ). 43 In contrast, significantly upregulated genes ( P < 0.00001) within the fibroblast population following distension included transcriptional promoters of cell proliferation and ECM proteins previously identified amongst the set of upregulated genes within the distended veins (Figure 4C), in addition to ECM-related genes laminin 2 subunit ( LAMA2 ), dystonin ( DST ), and BicC family RNA binding protein 1 ( BICC1 ). Interestingly, the roles of dystonin and BICC1 in vascular injury have not been previously investigated, but their functions as an anchor within the actin cytoskeleton and negative regulator of Wnt signaling, respectively, suggest that they may play an important role in modulating fibroblast motility and transdifferentiation, respectively, following vascular injury.…”

Section: Resultsmentioning

confidence: 91%

Integrated single-nuclei and spatial transcriptomic analysis reveals propagation of early acute vein harvest and distension injury signaling pathways following arterial implantation

Michaud,

Mota,

Bakhtiari

et al. 2023

Preprint

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BackgroundVein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. While previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on VGF. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury.MethodsEmploying a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing (snRNA-seq) and spatial transcriptomics (ST) analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24-hour after carotid-cartoid vein bypass implantation in a canine model (n=4).ResultsSpatial transcriptomic analysis of canine cephalic vein after initial conduit harvest and distention revealed significant enrichment of pathways (P< 0.05) involved in the activation of endothelial cells (ECs), fibroblasts (FBs), and vascular smooth muscle cells (VSMCs), namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and extracellular matrix (ECM) remodeling throughout the vein wall. Subsequent snRNA-seq analysis supported these findings and further unveiled distinct EC and FB subpopulations with significant upregulation (P< 0.00001) of markers related to endothelial injury response and cellular activation of ECs, FBs, and VSMCs. Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury-response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, includingVCAN(versican),FBN1(fibrillin-1), andVEGFC(vascular endothelial growth factor C), in addition to novel genes of interest such asGLIS3(GLIS family zinc finger 3) andEPHA3(ephrin-A3). These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such asIL-6,TGFBR1,SMAD4, andADAMTS9.By integrating the ST and snRNA-seq datasets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and FBs were notably enriched in the intima and media of distended veins. Lastly, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal transitioning ECs, protomyofibroblasts, and VSMCs in upregulating signaling pathways associated with cellular proliferation (MDK, PDGF, VEGF), transdifferentiation (Notch), migration (ephrin, semaphorin), ECM remodeling (collagen, laminin, fibronectin), and inflammation (thrombospondin), following distension.ConclusionsVein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies. This work highlights the first applications of single-nuclei and spatial transcriptomic analyses to investigate venous pathologies, underscoring the utility of these methodologies and providing a foundation for future investigations.

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“…It is unique since it has as many as 132 selenocysteines in its molecule, making it energetically costly to produce; however, it supplies tissues (such as the brain, kidney and testis) with selenium [ 122 ]. SeP also serves in antioxidant protection, which explains the fact that its reduced expression is observed in several types of tumours, including prostate, renal, hepatocellular or colorectal cancer [ 123 ]. Particularly noteworthy is the fact that during tumour development, a certain activity of the cells of the immune system is observed.…”

Section: Role Of Selenium In Inflammation and Immunitymentioning

confidence: 99%

“…Particularly noteworthy is the fact that during tumour development, a certain activity of the cells of the immune system is observed. It is also noted that SELENOP mRNA expression might be related to some immune functions, as it was positively correlated with immune marker genes for macrophage subtypes, including tumour-associated macrophages ( CD80, CD86 and HLA-G ), M1 macrophages ( CD36, IL-6 and NOS2 ), and M2 macrophages ( TGFβ, STAT6 and IL-10 ) in the following cancers: kidney clear cell carcinoma, brain lower grade glioma, lung adenocarcinoma and skin cutaneous melanoma [ 123 ]. SeP also reflects the selenium nutritional status in brain tissues, where it is the only selenium donor.…”

Section: Role Of Selenium In Inflammation and Immunitymentioning

confidence: 99%

“…A green upward-facing arrow ( ↑ ) indicates that Se has a stimulating effect, while a red downward-facing arrow ( ↓ ) indicates that Se has an inhibiting effect. Abbreviations: ROS—reactive oxygen species; GSSG:GSH—the ratio of oxidized to reduced glutathione; IL—interleukin; TNFα—tumour necrosis factor alpha; IFNγ—interferon gamma; NK—natural killer [ 52 , 119 , 120 , 123 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 ].…”

Section: Role Of Selenium In Inflammation and Immunitymentioning

confidence: 99%

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Selenium-Containing Agents Acting on Cancer—A New Hope?

et al. 2022

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Selenium-containing agents are more and more considered as an innovative potential treatment option for cancer. Light is shed not only on the considerable advancements made in understanding the complex biology and chemistry related to selenium-containing small molecules but also on Se-nanoparticles. Numerous Se-containing agents have been widely investigated in recent years in cancer therapy in relation to tumour development and dissemination, drug delivery, multidrug resistance (MDR) and immune system-related (anti)cancer effects. Despite numerous efforts, Se-agents apart from selenocysteine and selenomethionine have not yet reached clinical trials for cancer therapy. The purpose of this review is to provide a concise critical overview of the current state of the art in the development of highly potent target-specific Se-containing agents.

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A Pan-Cancer Analysis of the Role of Selenoprotein P mRNA in Tumorigenesis

Cited by 8 publications

References 54 publications

Therapeutic Benefits of Selenium in Hematological Malignancies

Therapeutic Benefits of Selenium in Hematological Malignancies

Integrated single-nuclei and spatial transcriptomic analysis reveals propagation of early acute vein harvest and distension injury signaling pathways following arterial implantation

Selenium-Containing Agents Acting on Cancer—A New Hope?

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