Expression Of Selenium-binding Protein 1 Research Articles

SELENBP1 Inhibits the Warburg Effect and Tumor Growth by Reducing the HIF1α Expression in Colorectal Cancer.

Colorectal cancer (CRC) is experiencing a significant increase in both incidence and mortality rates globally. The expression of Selenium-binding protein 1 (SELENBP1) has been reported to be notably downregulated in various malignancies, yet its biological functions and cellular mechanisms in CRC remain incompletely understood. In our investigation, we observed the downregulation of SELENBP1 in CRC tissues through quantitative real-time PCR and western blotting and identified a positive correlation between higher SELENBP1 expression and improved survival prognosis using Kaplan-Meier survival analysis. Through loss-of-function and gain-of-function studies, we demonstrated the tumor-suppressive roles of SELENBP1 in CRC, supported by results from both in vitro and in vivo experiments. Furthermore, we uncovered the pivotal functions of SELENBP1 in suppressing aerobic glycolysis in CRC cells by regulating glucose uptake, lactate generation, and extracellular acidification rate. At a mechanistic level, we found that SELENBP1 inhibits the expression of the key glycolytic modulator hypoxia-inducible factor 1 subunit alpha (HIF1α), and the inhibition of glycolysis by SELENBP1 can be reversed by ectopic expression of HIF1α. Therefore, our study highlights the potential of SELENBP1 as a promising target for CRC therapy, given its significant impact on tumor suppression and reprogrammed glucose metabolism. These findings contribute to a deeper understanding of the molecular mechanisms underlying CRC progression and may pave the way for the development of targeted therapies for this challenging disease.

SBP1 promotes tumorigenesis of thyroid cancer through TXN/NIS pathway

BackgroundAs the tissue with the highest selenium content in the body, the occurrence and development of thyroid cancer are closely related to selenium and selenoproteins. Selenium-binding protein 1 (SBP1) has been repeatedly implicated in several cancers, but its role and molecular mechanisms in thyroid cancer remains largely undefined.MethodsThe expression of SBP1, sodium/iodide symporter (NIS) and thioredoxin (TXN) were analyzed in clinical samples and cell lines. Cell counting kit-8 (CCK-8) and tube formation assays were used to analyze the cell viability and tube formation of cells. Immunofluorescence was used to determine the expression of the NIS. Co-immunoprecipitation (Co-IP) assay was carried out to verify the interaction of SBP1 with TXN. The mouse xenograft experiment was performed to investigate the growth of thyroid cancer cells with SBP1 knockdown in vivo.ResultsSBP1 was significantly increased in human thyroid cancer tissues and cells, especially in anaplastic thyroid cancer. Overexpression of SBP1 promoted FTC-133 cell proliferation, and the culture supernatant of SBP1-overexpression FTC-133 cells promoted tube formation of human retinal microvascular endothelial cells. Knockdown of SBP1, however, inhibited cell proliferation and tube formation. Furthermore, overexpression of SBP1 inhibited cellular differentiation of differentiated thyroid cancer cell line FTC-133, as indicated by decreased expression of thyroid stimulating hormone receptors, thyroglobulin and NIS. Knockdown of SBP1, however, promoted differentiation of BHT101 cells, an anaplastic thyroid cancer cell line. Notably, TXN, a negative regulator of NIS, was found to be significantly upregulated in human thyroid cancer tissues, and it was positively regulated by SBP1. Co-IP assay implied a direct interaction of SBP1 with TXN. Additionally, TXN overexpression reversed the effect of SBP1 knockdown on BHT101 cell viability, tube formation and cell differentiation. An in vivo study found that knockdown of SBP1 promoted the expression of thyroid stimulating hormone receptors, thyroglobulin and NIS, as well as inhibited the growth and progression of thyroid cancer tumors.ConclusionSBP1 promoted tumorigenesis and dedifferentiation of thyroid cancer through positively regulating TXN.

Selenium-binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non-small cell lung cancer.

Selenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium-containing protein as a mediator. Of note, the previous studies reported that the expression of selenium-binding protein 1 (SELENBP1) was obviously decreased in many human cancer tissues including non-small cell lung cancer (NSCLC). However, its roles in the origin and development of NSCLC are still unclear. The expression of SELENBP1 was measured by qRT-PCR, Western blotting and IHC in our collected clinical NSCLC tissues and cell lines. Next, the CCK-8, colony formation, wound-haeling, Millicell, Transwell, FCM assay, and in vivo xenograft model were performed to explore the function of SELENBP1 in NSCLC. The molecular mechanisms of SELENBP1 were investigated by Western blotting or IF assay. We further identified that the expression of SELENBP1 was significantly decreased in NSCLC tissues in TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues, as well as in four NSCLC cell lines compared with normal lung cells. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT-II) cells for the first time. Then, a series of in vitro experiments uncovered that overexpression of SELENBP1 inhibited the proliferation, migration, and invasion of NSCLC cells, and induced cell apoptosis. Moreover, overexpression of SELENBP1 also inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells in part via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1 inducing the apoptosis of NSCLC cells was associated with the activation of caspase-3 signaling pathway under nonhigh level of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis might be related to its combining with GPX1 and colocalizing in the nucleus under high level of oxidative stress. Our findings highlighted that SELENBP1 was an important tumor suppressor during the origin and development of NSCLC. It may help to discover novel biomarkers or drug therapy targets for NSCLC.

Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is associated with immunotherapy efficacy and survival in colorectal cancer

BackgroundSelenium-binding protein 1 (SELENBP1), a member of the selenium-containing protein family, plays an important role in malignant tumorigenesis and progression. However, it is currently lacking research about relationship between SELENBP1 and immunotherapy in colorectal cancer (CRC).MethodsWe first analyzed the expression levels of SELENBP1 based on the Cancer Genome Atlas (TCGA), Oncomine andUALCAN. Chisq.test, Fisher.test, Wilcoxon-Mann-Whitney test and logistic regression were used to analyze the relationship of clinical characteristics with SELENBP1 expression. Then Gene ontology/ Kyoto encyclopedia of genes and genomes (GO/KEGG), Gene set enrichment analysis (GSEA) enrichment analysis to clarify bio-processes and signaling pathways. The cBioPortal was used to perform analysis of mutation sites, types, etc. of SELENBP1. In addition, the correlation of SELENBP1 gene with tumor immune infiltration and prognosis was analyzed using ssGSEA, ESTIMATE, tumor immune dysfunction and rejection (TIDE) algorithm and Kaplan-Meier (KM) Plotter database. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to validate the expression of SELENBP1 in CRC samples and matched normal tissues. Immunohistochemistry (IHC) was further performed to detect the expression of SELENBP1 in CRC samples and matched normal tissues.ResultsWe found that SELENBP1 expression was lower in CRC compared to normal colorectal tissue and was associated with poor prognosis. The aggressiveness of CRC increased with decreased SELENBP1 expression. Enrichment analysis showed that the SELENBP1 gene was significantly enriched in several pathways, such as programmed death 1 (PD-1) signaling, signaling by interleukins, TCR signaling, collagen degradation, costimulation by the CD28 family. Decreased expression of SELENBP1 was associated with DNA methylation and mutation. Immune infiltration analysis identified that SELENBP1 expression was closely related to various immune cells and immune chemokines/receptors. With increasing SELENBP1 expression, immune and stromal components in the tumor microenvironment were significantly decreased. SELENBP1 expression in CRC patients affects patient prognosis by influencing tumor immune infiltration. Beside this, SELENBP1 expression is closely related to the sensitivity of chemotherapy and immunotherapy.ConclusionsSurvival analysis as well as enrichment and immunoassay results suggest that SELENBP1 can be considered as a promising prognostic biomarker for CRC. SELENBP1 expression is closely associated with immune infiltration and immunotherapy. Collectively, our study provided useful information on the oncogenic role of SELENBP1, contributing to further exploring the underlying mechanisms.

SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial-mesenchymal transition.

Selenium-binding protein 1 (SELENBP1) is frequently dysregulated in various malignancies including colorectal cancer (CRC); however, its roles in progression of CRCs and the underlying mechanism remain to be elucidated. In this study, we compared the expression of SELENBP1 between CRCs and colorectal normal tissues (NTs), as well as between primary and metastatic CRCs; we determined the association between SELENBP1 expression and CRC patient prognoses; we conducted both in vitro and in vivo experiments to explore the functional roles of SELENBP1 in CRC progression; and we characterized the potential underlying mechanisms associated with SELENBP1 activities. We found that the expression of SELENBP1 was significantly and consistently decreased in CRCs than that in adjacent NTs, while significantly and frequently decreased in metastatic than primary CRCs. High expression of SELENBP1 was an independent predictor of favorable prognoses in CRC patients. Overexpression of SELENBP1 suppressed, while silencing of SELENBP1 promoted cell proliferation, migration and invasion, and in vivo tumorigenesis of CRC. Mechanically, SELENBP1 may suppress CRC progression by inhibiting the epithelial–mesenchymal transition.

SELENBP1 Inhibits Cell Proliferation and Migration in Colorectal Cancers by Suppressing EMT

Background: Selenium binding protein 1 (SELENBP1) is frequently dysregulated in various malignancies including colorectal cancer (CRC). Methods: Expression of SELENBP1 in colorectal normal tissues (NTs) and CRCs was determined using bioinformatics data and clinical samples. Correlation between SELENBP1 expression and patient survival was evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate survival analyses were conducted with a Cox proportional hazards regression model. The impact of SELENBP1 on cell proliferation, migration and invasion, and in vivo tumorigenesis were investigated by Cell Counting Kit-8 (CCK8) assay and EdU assay, Transwell migration and invasion assays, and a subcutaneous xenograft model. The underlying mechanism was characterized for the suppressive roles of SELENBP1 in CRC carcinogenesis and progression. Findings: The expression of SELENBP1 was significantly and consistently decreased in CRCs than that in NTs, while significantly and frequently decreased in metastatic than primary CRCs. High expression of SELENBP1 was an independent predictor of favorable prognoses in CRC patients. Overexpression of SELENBP1 suppressed, while silencing of SELENBP1 promoted cell proliferation, migration and invasion, and in vivo tumorigenesis of CRC. Mechanically, SELENBP1 may suppress CRC carcinogenesis and progression by inhibiting the epithelial-mesenchymal transition (EMT). Interpretation: our results demonstrate that SELENBP1 could be a promising tumor suppressor which should be further investigated. Funding: This work was supported by Shanghai Fifth People’s Hospital (grant numbers 2016WYRC01 and 2017WYRCSG01); the Medical System of Shanghai Minhang District (grant number 2017MWDXK01); the Shanghai Minhang District Health and Family Planning Commission (grant number 2016MW03); and the Shanghai Minhang District Science and Technology Commission (grant numbers 2017MHZ02, 2019MHZ054, and 2020MHZ080). Declaration of Interest: The authors declare no competing interests. Ethical Approval: This study was approved by the Institutional Ethics Committee at Shanghai Fifth People’s Hospital and adhered to the principles listed in the Declaration of Helsinki.

Silencing of selenium-binding protein disrupted the active immunization of the termite Reticulitermes chinensis and improved the lethal effect of the entomopathogenic fungus Metarhizium anisopliae

Active immunization is a process by which naïve termites receive sublethal doses of pathogenic spores from infected termites through social contact to enhance their immune responses; this process significantly diminishes the termite biocontrol effect of commercial entomopathogenic products, such as Metarhizium anisopliae. We found that the expression of selenium-binding protein (SeBP) was significantly increased by active immunization of the nestmates of fungus-contaminated termites, suggesting a close relationship between SeBP and active immunization in termites. To elucidate this relationship, we used the fungus M. anisopliae to contaminate the termite Reticulitermes chinensis and then measured the changes in the grooming behavior, antifungal activity, immune gene expression and survival of the double-stranded SeBP (dsSeBP)-injected nestmates of these fungus-contaminated termites. Our results showed that there was no significant change in the grooming behavior of the dsSeBP-injected nestmates of the fungus-contaminated termites, but the antifungal activity and expression of the immune gene Gram-negative bacteria-binding protein 2 (GNBP2) were significantly reduced. Moreover, the survival of the dsSeBP-injected nestmates of the fungus-contaminated termites was significantly decreased. These findings showed that SeBP knockdown disrupted the active immunization of R. chinensis and improved the lethal effect of M. anisopliae, which suggested that enhancing immune dysregulation by targeting SeBP was a sound strategy for the biological control of termites.

Transcriptome, proteome, and metabolome reveal the mechanism of tolerance to selenate toxicity in Cardamine violifolia

Cardamine violifolia was found here to accumulate selenium (Se) to over 9000 mg kg−1 dry weight. To investigate the mechanism of Se accumulation and tolerance in C. violifolia, metabolome, transcriptome, and proteome technologies were applied to C. violifolia seedlings treated with selenate. Several sulfate transporter (Sultr) genes (Sultr1;1, Sultr1;2, and Sultr2;1) and sulfur assimilatory enzyme genes showed high expression levels in response to selenate. Many calcium protein and cysteine-rich kinase genes of C. violifolia were downregulated, whereas selenium-binding protein 1 (SBP1) and protein sulfur deficiency-induced 2 (SDI2) of C. violifolia were upregulated by selenate. The expression of genes involved in the ribosome and posttranslational modifications and chaperones in C. violifolia were also detected in response to selenate. Based on the results of this study and previous findings, we suggest that the downregulated expression of calcium proteins and cysteine-rich kinases, and the upregulated expression of SBP1 and SDI2, were important contributors to the Se tolerance of C. violifolia. The downregulation of cysteine-rich kinases and calcium proteins would enhance Se tolerance of C. violifolia is a novel proposition that has not been reported on other Se hyperaccumulators. This study provides us novel insights to understand Se accumulation and tolerance in plants.

Selenium-binding protein 1 transcriptionally activates p21 expression via p53-independent mechanism and its frequent reduction associates with poor prognosis in bladder cancer

BackgroundRecent studies have shown that selenium-binding protein 1 (SELENBP1) is significantly down-regulated in a variety of solid tumors. Nevertheless, the clinical relevance of SELENBP1 in human bladder cancer has not been described in any detail, and the molecular mechanism underlying its inhibitory role in cancer cell growth is largely unknown.MethodsSELENBP1 expression levels in tumor tissues and adjacent normal tissues were evaluated using immunoblotting assay. The association of SELENBP1 expression, clinicopathological features, and clinical outcome was determined using publicly available dataset from The Cancer Genome Atlas bladder cancer (TCGA-BLCA) cohort. DNA methylation in SELENBP1 gene was assessed using online MEXPRESS tool. We generated stable SELENBP1-overexpression and their corresponding control cell lines to determine its potential effect on cell cycle and transcriptional activity of p21 by using flow cytometry and luciferase reporter assay, respectively. The dominant-negative mutant constructs, TAM67 and STAT1 Y701F, were employed to define the roles of c-Jun and STAT1 in the regulation of p21 protein.ResultsHere, we report that the reduction of SELENBP1 is a frequent event and significantly correlates with tumor progression as well as unfavorable prognosis in human bladder cancer. By utilizing TCGA-BLCA cohort, DNA hypermethylation, especially in gene body, is shown to be likely to account for the reduction of SELENBP1 expression. However, an apparent paradox is observed in its 3′-UTR region, in which DNA methylation is positively related to SELENBP1 expression. More importantly, we verify the growth inhibitory role for SELENBP1 in human bladder cancer, and further report a novel function for SELENBP1 in transcriptionally modulating p21 expression through a p53-independent mechanism. Instead, ectopic expression of SELENBP1 pronouncedly attenuates the phosphorylation of c-Jun and STAT1, both of which are indispensable for SELENBP1-mediated transcriptional induction of p21, thereby resulting in the G0/G1 phase cell cycle arrest in bladder cancer cell.ConclusionsTaken together, our findings provide clinical and molecular insights into improved understanding of the tumor suppressive role for SELENBP1 in human bladder cancer, suggesting that SELENBP1 could potentially be utilized as a prognostic biomarker as well as a therapeutic target in future cancer therapy.

Abstract P4-04-18: Estrogen receptor α-dependent transcriptional induction of selenium-binding protein 1 increases the sensitivity of tamoxifen treatment in breast cancer

Abstract Reduction of selenium-binding protein 1 (SELENBP1) has been frequently observed in various solid tumors, and associated with poor clinical prognosis, implicating SELENBP1 as a potential tumor suppressor. However, the molecular mechanism underlying the transcriptional regulation of SELENBP1 remains poorly understood. In this study, we first analyzed the relationship between SELENBP1 mRNA levels and clinical or pathological features of breast cancer in METABRIC datasets, and found that SELENBP1 mRNA levels were differentially expressed in PAM50 molecular subtypes with highest levels in Luminal A/B subtype and lowest levels in Basal-like/Claudin-low subtype, indicating that SELENBP1 might function as the downstream player of estrogen receptor α (ERα). Following the adjustment of clinicopathological characteristics including the menopausal status, ER/HR/ERBB2 status, TNM stage and histological grade, the Kaplan-Meier survival analysis surprisingly showed that patients with higher levels of SELENBP1 mRNA (n=43) had shorter survival time than those with moderate levels of SELENBP1 expression (n=102) in Luminal A subtype (Hazard Ratio 1.59; 95% CI 0.99-2.54; Logrank p=0.0367), although the patients with lower SELENBP1 levels were consistent the poor prognosis in Basal-like/Claudin-low subtype (Hazard Ratio 1.54; 95% CI 0.97-2.44; Logrank p=0.0356). To elucidate this controversy, we knocked down the expression of ERα in MCF-7 cells using shRNA targeting ERα, and found that knockdown of ERα resulted in the down-regulation of mRNA and protein expression of SELENBP1. In addition, SELENBP1 promoter-driven luciferase reporter assay reveled ERα regulated the expression of SELENBP1 at transcriptional level. Interestingly, we further found that the addition of 4-hydroxytamoxifen (4-OHT) led to a dramatic reduction of SELENBP1 protein expression in MCF-7 cells, while forced expression of SELENBP1 in MCF-7 cells significantly enhanced 4-OHT-mediated inhibition of anchor-independent cancer cell growth. Collectively, these results suggested that the transcriptional induction of SELENBP1 by ERα might function as a downstream tumor suppressor in breast cancer cells, but endocrine therapy led to the down-regulation of SELENBP1 expression due to the blocking of ERα signaling in the patients with Luminal subtype, which was likely to explain the observation of differential predictive value for SELENBP1 mRNA levels in the Luminal and Basal-like/Claudin-low subtypes. Further investigation in vitro and in vivo has been ongoing in our laboratory, and the results from which will help us better understand the clinical relevance for SELENBP1 as a promising therapeutic target in improving the efficacy of endocrine therapy. This study was supported in part by National Natural Science Foundation of China (8160111571) and Guangdong Natural Science Foundation (2016A030313768). Citation Format: Liao N, Wang Y, Zhang G, Cao L, Li K, Ren C-Y, Wen L-Z, Shi Y, Zhu W, Chen X. Estrogen receptor α-dependent transcriptional induction of selenium-binding protein 1 increases the sensitivity of tamoxifen treatment in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-18.

Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis.

Selenium binding protein1 (SELENBP1) has been associated with several cancers. Its exact role was unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to MTO of methylotrophic bacteria, converting methanethiol to H2O2, formaldehyde and H2S, an activity not known to exist in humans. Mutations in SELENBP1 were found in five patients with a cabbage-like smelling breath. Increased levels of methanethiol and dimethylsulfide are the main odorous compounds in their breath and responsible for the malodor. Increased urinary excretion of dimethylsulfoxide is a diagnostic biomarker of MTO-deficiency. Patient fibroblasts showed reduced amounts of SELENBP1 protein and deficient MTO enzymatic activity which could be restored by lentiviral-mediated expression of the wild-type SELENBP1 gene. A knockout mouse line showed the same biochemical characteristics. Our data define a novel inborn error of metabolism caused by MTO-deficiency leading to a malodor syndrome. MTO deficiency may be a frequent inborn error of metabolism.

Selenium-binding protein 1 in head and neck cancer is low-expression and associates with the prognosis of nasopharyngeal carcinoma.

Background:Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis.Methods:SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1.Results:Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group.Conclusion:SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis.

Elevated expression of SLC34A2 inhibits the viability and invasion of A549 cells.

Abnormal expression of solute carrier family 34 (sodium phosphate), member 2 (SLC34A2) in the lung may induce abnormal alveolar type II (AT II) cells to transform into lung adenocarcinoma cells, and may also be important in biological process of lung adenocarcinoma. However, at present, the effects and molecular mechanisms of SLC34A2 in the initiation and progression of lung cancer remain to be elucidated. To the best of our knowledge, the present study revealed for the first time that the expression levels of SLC34A2 were downregulated in the A549 and H1299 lung adenocarcinoma cell lines. Further investigation demonstrated that the elevated expression of SLC34A2 in A549 cells was able to significantly inhibit cell viability and invasion in vitro. In addition, 10 upregulated genes between the A549-P-S cell line stably expressing SLC34A2 and the control cell line A549-P were identified by microarray analysis and quantitative polymerase chain reaction, including seven tumor suppressor genes and three complement genes. Furthermore, the upregulation of complement gene C3 and complement 4B preproprotein (C4b) in A549-P-S cells was confirmed by ELISA analysis and was identified to be correlated with recovering Pi absorption in A549 cells by the phosphomolybdic acid method by enhancing the expression of SLC34A2. Therefore, it was hypothesized that the mechanisms underlying the effect of SLC34A2 on A549 cells might be associated with the activation of the complement alternative pathway (C3 and C4b) and upregulation of the expression of selenium binding protein 1, thioredoxin-interacting protein, PDZK1-interacting protein 1 and dual specificity protein phosphatase 6. Downregulation of SLC34A2 may primarily cause abnormal AT II cells to escape from complement-associated immunosurveillance and abnormally express certain tumor-suppressor genes inducing AT II cells to develop into lung adenocarcinoma. The present study further elucidated the effects and mechanisms of SLC34A2 in the generation and development of lung cancer.

Chronic Allograft Vasculopathy Correlates with the Downregulation of Selenium-Binding Protein 1 in Smooth Muscle Cells

Selenium binding protein-1 (SBP-1) has been implicated in intracellular protein trafficking and secretion. In a rhesus monkey kidney transplant model we previously demonstrated that SBP-1 is significantly downregulated in the smooth muscle cells (SMC) of arteries with chronic allograft vasculopathy (CAV). The purposes of this study were multiple: (1) to investigate the expression of SBP-1 in human and murine allografts with chronic vasculopathy; (2) to explore factors that …

The Function and Significance of SELENBP1 Downregulation in Human Bronchial Epithelial Carcinogenic Process

BackgroundOur quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1) was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC) carcinogenesis.MethodsiTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium) from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(a)pyrene (B[a]P)-induced human bronchial epithelial cell transformation were determined.Results102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation.ConclusionsThe present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.

Decreased Selenium-Binding Protein 1 Enhances Glutathione Peroxidase 1 Activity and Downregulates HIF-1α to Promote Hepatocellular Carcinoma Invasiveness

We aimed to characterize the role of selenium-binding protein 1 (SBP1) in hepatocellular carcinoma (HCC) invasiveness and underlying clinical significance. SBP1 expression was measured in stepwise metastatic HCC cell lines by Western blotting. The role of SBP1 in HCC was investigated using siRNA. Immunofluorescence analyses were used to detect the interaction between SBP1 and glutathione peroxidase 1 (GPX1). Nineteen fresh tumor tissues and 323 paraffin-embedded samples were used to validate in vitro findings and to detect the prognostic significance of SBP1, respectively. Inhibition of SBP1 effectively increased cell motility, promoted cell proliferation, and inhibited apoptosis only under oxidative stress; it also greatly enhanced GPX1 activity without altering GPX1 expression and downregulated hypoxia-inducible factor-1α (HIF-1α) expression. SBP1 and GPX1 formed nuclear bodies and colocalized under oxidative stress. In freshly isolated clinical HCC tissues, decreased SBP1 was linked with increased GPX1 activity and correlated with vascular invasion. Tumor tissue microarrays indicated that SBP1 was an independent risk factor for overall survival and disease recurrence; patients with lower SBP1 expression experienced shorter overall survival periods and higher rates of disease recurrence (P < 0.001). Further analyses indicated that the predictive power of SBP1 was more significant for patients beyond the Milan criteria than patients within the Milan criteria. Decreased expression of SBP1 could promote tumor invasiveness by increasing GPX1 activity and diminishing HIF-1α expression in HCC; SBP1 could be a novel biomarker for predicting prognosis and guiding personalized therapeutic strategies, especially in patients with advanced HCC.

Expression and clinical significance of selenium binding protein 1 in gastric cancer

Objective To detect the expression of selenium binding protein 1 ( SBP1 ) in gastric cancer cell line SGC7901, BGC823, normal gastric epithelial cell line GES-1, gastric cancer tissues and normal gastric tissues, explore the relationship between SBP1 and pathologic features, and discuss the feasibility of SBP1 as an diagnostic marker of gastric cancer. Methods The clinical data of 135 patients with gastric cancer who were admitted to Zhongnan Hospital of Wuhan University from 2006 to 2007 were retrospectively analyzed. The expression of SBP1 in the gastric cancer tissues and 16 cases of normal gastric tissues were detected by immunohistochemistry. The mRNA and protein expressions of SBP1 of SGC7901, BGC823 and GES-1 were determined by Western blot and RT-PCR. All data were analyzed by using chi-square test and one-way analysis of variance.Results The mRNA expressions of SBP1 in BGC823 and SGC7091 were 0. 120 ± 0. 020 and 0. 133 ± 0. 015,respectively, which were significantly lower than 0. 907 ± 0. 015 in GES-1 ( F = 2106. 462, P ＜ 0.05 ). The protein expression of SBP1 in BGC823 and SGC7901 were 0.253 ±0.015 and 0.273 ±0.015 ,respectively, which were significantly lower than 0.877 ±0.025 in GES-1 ( F = 1026. 758, P ＜0.05 ). A strong positive reaction of SBP1 was observed in 3 cases of gastric cancer tissues and 16 cases of normal gastric tissues. The decrease of the protein expression of SBP1 was correlated with clinical stages of the patients ( x2 = 12. 629, P ＜ 0.05 ), rather than the sexes, ages, tumor histological types, tumor differentiation, infiltration depths and lymph node metastasis (x2 =2. 142, 0.860, 1.838, 5.001,4.858, 1.994, P＞0. 05). Conclusions The decrease of SBP1 expression could be used as a marker in diagnosing gastric cancer. Down-regulation of SBP1 expression may play an important role in the genesis and prognosis of gastric cancer. Key words: Gastric neoplasms; Selenium binding protein 1; Immunohistochemistry

Altered expression of selenium-binding protein 1 in gastric carcinoma and precursor lesions

Selenium-binding protein 1 (SBP1) has been shown to be greatly reduced in various human cancers. The purpose of this study was to evaluate the expression of SBP1 in precursor lesions and gastric carcinoma (GC) and to discuss the specific role of SBP1 in gastric carcinogenesis. Using tissue microarray (TMA) technology and immunohistochemical (IHC) survey, SBP1 expressions were evaluated based on a semi-quantitative scoring system developed for this study in 25 paired of GC and corresponding nonneoplastic epithelia tissues, 21 gastric ulcer, 13 gastric polyp, 19 chronic atrophic gastritis, 20 intestinal metaplasia, and 16 dysplasia tissues. We found abundant expression of SBP1 in most precursor lesions in addition to the nonneoplastic epithelia tissues. However, the expression of SBP1 was severely suppressed in most of the GC tissues (P=0.000). Although no statistical differences were found between the expressions of SBP1 in gastric tissues with different levels of intestinal metaplasia or dysplasia (P>0.05), the reduction in SBP1 seems to be correlated with clinical stage of GC (P=0.044). Thus, SBP1 can be supposed as a diagnosis marker of GC. The suppression of SBP1 may be a late event in gastric carcinogenesis.

Reduced selenium-binding protein 1 is associated with poor survival rate in gastric carcinoma

Human selenium-binding protein 1 (SBP1) is known to play a key role in the development and progression of many cancers. The role of SBP1 expression in gastric carcinoma (GC) is far from being fully established. The aim of the present study was to evaluate the expression of SBP1 in GC and correlate the findings with several clinicopathological features and prognosis. Tissue samples from 65 patients treated by gastric resection for GC with clinical stage II and III were used. Each sample was matched with the corresponding nonneoplastic epithelia tissues removed during the same surgery. Reverse transcriptase-polymerase chain reaction, immunostaining and Western blot analyses were used to detect the expression of SBP1 at the mRNA and protein levels, respectively. The associations between SBP1 expressions and clinicopathological features were analyzed. Expressions of SBP1 at both mRNA and protein levels were significantly lower in GC than those in the corresponding nonneoplastic epithelia tissues (P = 0.000). SBP1-negative expression had a significant relationship with high clinical stage (P = 0.038). Prognosis of SBP1-negative patients was significantly poorer than that of SBP1-positive patients (P = 0.001), and multivariate analysis further confirmed that SBP1 was an independent prognostic factor (P = 0.004). Thus, down-regulation of SBP1 may play a key role in the tumorigenic process of human GC. The correlation of SBP1 reduction in GC with clinical stage and survival proposes a prognostic role in GC.

Arabidopsis putative selenium-binding protein1 expression is tightly linked to cellular sulfur demand and can reduce sensitivity to stresses requiring glutathione for tolerance.

Selenium-Binding Protein1 (SBP1) gene expression was studied in Arabidopsis (Arabidopsis thaliana) seedlings challenged with several stresses, including cadmium (Cd), selenium {selenate [Se(VI)] and selenite [Se(IV)]}, copper (Cu), zinc (Zn), and hydrogen peroxide (H(2)O(2)) using transgenic lines expressing the luciferase (LUC) reporter gene under the control of the SBP1 promoter. In roots and shoots of SBP1LUC lines, LUC activity increased in response to Cd, Se(VI), Cu, and H(2)O(2) but not in response to Se(IV) or Zn. The pattern of expression of SBP1 was similar to that of PRH43, which encodes the 5'-Adenylylphosphosulfate Reductase2, a marker for the induction of the sulfur assimilation pathway, suggesting that an enhanced sulfur demand triggers SBP1 up-regulation. Correlated to these results, SBP1 promoter showed enhanced activity in response to sulfur starvation. The sulfur starvation induction of SBP1 was abolished by feeding the plants with glutathione (GSH) and was enhanced when seedlings were treated simultaneously with buthionine sulfoxide, which inhibits GSH synthesis, indicating that GSH level participates in the regulation of SBP1 expression. Changes in total GSH level were observed in seedlings challenged with Cd, Se(VI), and H(2)O(2). Accordingly, cad2-1 seedlings, affected in GSH synthesis, were more sensitive than wild-type plants to these three stresses. Moreover, wild-type and cad2-1 seedlings overexpressing SBP1 showed a significant enhanced tolerance to Se(VI) and H(2)O(2) in addition to the previously described resistance to Cd, highlighting that SBP1 expression decreases sensitivity to stress requiring GSH for tolerance. These results are discussed with regard to the potential regulation and function of SBP1 in plants.