SERPINB3 (serpin peptidase inhibitor, clade B (ovalbumin), member 3).
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ABSTRACT:
SUBMITTER: Turato C
PROVIDER: S-EPMC4430857 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
SERPINB3 (serpin peptidase inhibitor, clade B (ovalbumin), member 3).
Turato Cristian C Pontisso Patrizia P
Atlas of genetics and cytogenetics in oncology and haematology 20150101 3
Review on SERPINB3, with data on DNA/RNA, on the protein encoded and where the gene is implicated. ...[more]
Similar Datasets
Project description:BackgroundIn a previous study, we reported that serpin peptidase inhibitor clade A member 1 (serpinA1) is upregulated in Snail-overexpressing gastric cancer. Although serpinA1 has been studied in several types of cancer, little is known about its roles and mechanisms of action. In this study, we examined the role of serpinA1 in the migration and invasion of gastric cancers and determined its underlying mechanism.MethodsExpression levels were assessed by western blot analyses and real-time PCR. Snail binding to serpinA1 promoter was analysed by chromatin immunoprecipitation (ChIP) assays. The roles of serpinA1 were studied using cell invasion and migration assays. In addition, the clinicopathologic and prognostic significance of serpinA1 expression were validated in 400 gastric cancer patients using immunohistochemical analysis.ResultsOverexpression of Snail resulted in upregulation of serpinA1 in gastric cancer cell lines, AGS and MKN45, whereas knockdown of Snail inhibited serpinA1 expression. Chromatin immunoprecipitation analysis showed that overexpression of Snail increased Snail recruitment to the serpinA1 promoter. Overexpression of serpinA1 increased the migration and invasion of gastric cancer cells, whereas knockdown of serpinA1 decreased invasion and migration. Moreover, serpinA1 increased mRNA levels and release of metalloproteinase-8 in gastric cancer cells. Serpin peptidase inhibitor clade A member 1 was observed in the cytoplasm of tumour cells and the stroma by immunohistochemistry. Enhanced serpinA1 expression was significantly associated with increased tumour size, advanced T stage, perineural invasion, lymphovascular invasion, lymph node metastases, and shorter overall survival.ConclusionsSerpin peptidase inhibitor clade A member 1 induces the invasion and migration of gastric cancer cells and its expression is associated with the progression of gastric cancer. These results may provide a potential target to prevent invasion and metastasis in gastric cancer.
| S-EPMC4229634 | biostudies-literature
Project description:BackgroundRecent studies have revealed that serpin peptidase inhibitor clade E member 2 (SERPINE2) is associated with tumorigenesis. However, SERPINE2 expression and its role in lung adenocarcinomas are still unknown.MethodsThe expression levels of SERPINE2 in 74 consecutively resected lung adenocarcinomas were analyzed by using immunostaining. Inhibition of SERPINE2 expression by small interfering RNA (siRNA) was detected by quantitative PCR. Cell number assays and cell apoptosis assays were performed to clarify the cell-autonomous function of SERPINE2 in A549 and PC9 lung cancer cells.ResultsThe overall survival of patients with high SERPINE2 expression was significantly worse than that of patients with low SERPINE2 expression (P = 0.0172). Multivariate analysis revealed that SERPINE2 expression was an independent factor associated with poor prognosis (P = 0.03237). The interference of SERPINE2 decreased cell number and increased apoptosis in A549 and PC9 cells CONCLUSION: These results suggest that SERPINE2 can be used as a novel prognostic marker of lung adenocarcinoma.
| S-EPMC7737331 | biostudies-literature
Project description:Background/purposeThe serpin peptidase inhibitor, clade E, member 2 (SERPINE2), is upregulated in breast cancer, prostate cancer, and urothelial carcinoma; however, limited information exists regarding its expression in oral cancer. Therefore, this study aimed to analyze the association between SERPINE2 expression and oral squamous cell carcinoma (OSCC) outcomes.Materials and methodsSERPINE2 mRNA and protein expression in patients with head and neck squamous cell carcinoma and OSCC were investigated using online databases and tissue-array analysis. Its relationship with clinicopathological characteristics, OSCC prognosis and its biological function in OSCC cells were explored.ResultsAnalysis using online databases revealed higher SERPINE2 expression in tumor tissues and its role as a prognostic factor. High SERPINE2 protein levels were significantly correlated with adverse pathological parameters, including advanced clinical stage and tumor status (P < 0.001), lymph nodes (P = 0.014), and distant metastases (P = 0.013). High SERPINE2 expression was associated with worse overall survival (P < 0.001) and was identified as an independent prognostic factor for OSCC. In vitro studies revealed that SERPINE2 knockdown significantly reduced cell proliferation, migration, and invasion in OSCC cell lines.ConclusionThis study suggests that SERPINE2 may serve as a prognostic biomarker and potential therapeutic target for oral cancer.
| S-EPMC10829680 | biostudies-literature
Project description:Gastric cancer is the second most common cause of cancer-associated death in Asia. The incidence and mortality rates of gastric cancer have markedly increased in the past few decades. Therefore, the identification of novel gastric cancer biomarkers are needed to determine prognosis. The role of serpin peptidase inhibitor clade A member 1 (SERPINA1) has been studied in several types of cancer; however, little is known about its mechanism in gastric cancer. The present study aimed to evaluate SERPINA1 as a potential prognostic biomarker in gastric cancer and to identify the possible mechanisms underlying its action. The expression levels of SERPINA1 in several gastric cancer datasets were assessed, and it was identified that high expression of SERPINA1 was associated to poor clinical outcomes. Furthermore, using histochemical analysis, western blotting, apoptotic analysis, gap closure and invasion assays in cell lines, it was reported that silencing of SERPINA1 inhibited the formation of cellular pseudopodia and did not affect apoptosis, but promoted cell cycle S-phase entry. In addition, overexpression of SERPINA1 increased the migration and invasion of gastric cancer cells, whereas knockdown of SERPINA1 decreased these functions. Moreover, SERPINA1 overexpression increased the protein levels of SMAD4, which is a key regulator of the transforming growth factor (TGF)-β signaling pathway. Taken together, the present data demonstrated that SERPINA1 promotes gastric cancer progression through TGF-β signaling, and suggested that SERPINA1 may be a novel prognostic biomarker from tumor tissue biopsy in gastric cancer.
| S-EPMC7520747 | biostudies-literature
Project description:BackgroundSARS-CoV-2 has a number of targets, including the kidneys. Acute Kidney Injury (AKI) might develop in up to a quarter of SARS-CoV-2 patients. In the clinical environment, AKI is linked to a high rate of death and leads to the progression of AKI to chronic renal disease.AimWe aimed to investigate rs2093266 and rs1955656 polymorphisms in SERPINA4 and SERPINA5 genes, respectively, as risk factors for COVID-19 induced AKI.Subjects and methodsA case-control study included 227 participants who were divided into three groups: 81 healthy volunteers who served as controls, 76 COVID-19 patients without AKI and 70 COVID -19 patients with AKI. The TaqMan assay was used for genotyping the SERPINA4 (rs2093266) and SERPINA5 (rs1955656) polymorphisms by real-time PCR technique.ResultsLymphocytes and eGFR showed a significantly decreasing trend across the three studied groups, while CRP, d-Dimer, ferritin, creatinine, KIM-1and NGAL showed a significantly increasing trend across the three studied groups (P < 0.001). Rs2093266 (AG and AA) genotypes were significant risk factors among non-AKI and AKI groups in comparison to controls. Rs1955656 (AG and AA) were significant risk factors among the AKI group, while AA was the only significant risk factor among the non-AKI group. Recessive, dominant, co-dominant, and over-dominant models for genotype combinations were demonstrated. The GG v AA, GG + AG v AA, and GG v AG + AA models of the rs2093266 were all significant predictors of AKI, whilst only the GG v AA model of the rs1955656 SNP was a significant predictor. The logistic regression model was statistically significant, χ2 = 56.48, p < 0.001. AKI was associated with progressed age (OR = 0.95, 95% CI: 0.91-0.98, p = 0.006), suffering from chronic diseases (OR = 3.25, 95% CI: 1.31-8.01, p = 0.010), increased BMI (OR = 0.89, 95% CI: 0.81-0.98, p = 0.018), immunosuppressive (OR = 4.61, 95% CI: 1.24-17.16, p = 0.022) and rs2093266 (AG + AA) (OR = 3.0, 95% CI: 1.11-8.10, p = 0.030).ConclusionSingle nucleotide polymorphisms (rs2093266) at SERPINA4 gene and (rs1955656) at SERPINA5 gene were strongly linked to the development of AKI in COVID-19 patients.
| S-EPMC8915573 | biostudies-literature
Project description:Serpin superfamily proteins, most of which are serine protease inhibitors, share an unusual mechanism rooted in their conserved metastable tertiary structure. Although serpins have been identified in isolated members of archea, bacteria, and plants, a remarkable expansion is found in vertebrates. The chicken protein ovalbumin, a storage protein from egg white, lacking protease inhibitory activity, is an historical member of the superfamily and the founding member of the subgroup known as ov-serpins (ovalbumin-related serpins) or clade B serpins. In the human, ov-serpins include 13 proteins involved in the regulation of inflammation, apoptosis, angiogenesis, and embryogenesis. Here, a detailed analysis of the chicken (Gallus gallus) genome identified 10 clade B serpin genes that map to a single approximately 150-kb locus and contain the signature protein sequence of serpins and the gene structure of ov-serpins, with either seven or eight exons. Orthologues of PAI-2 (SERPINB2), MNEI (SERPINB1), PI-6 (SERPINB6), and maspin (SERPINB5) are highly conserved. Comparison with human ov-serpins identified avian-specific and mammal-specific genes. Importantly, a unique model of mammalian ov-serpin evolution is revealed from the comparative analysis of the chicken and human loci. The presence of a subset of ov-serpin genes in zebrafish (Danio rerio) gives insight into the ancestral locus. This comparative genomic study provides a valuable perspective on the evolutionary pathway for the clade B serpins, allowing the identification of genes with functions that may have been conserved since the origin of vertebrates. In addition, it suggests that "newer" serpins, such as ovalbumin, have contributed to vertebrate adaptation.
| S-EPMC1183561 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. The serpin peptidase inhibitor SERPINB5 is a tumour-suppressor gene that promotes the development of various cancers in humans. However, whether SERPINB5 gene variants play a role in HCC susceptibility remains unknown. In this study, we genotyped 6 SNPs of the SERPINB5 gene in an independent cohort from a replicate population comprising 302 cases and 590 controls. Additionally, patients who had at least one rs2289520 C allele in SERPINB5 tended to exhibit better liver function than patients with genotype GG (Child-Pugh grade A vs. B or C; P?=?0.047). Next, haplotype blocks were reconstructed according to the linkage disequilibrium structure of the SERPINB5 gene. A haplotype "C-C-C" (rs17071138?+?rs3744941?+?rs8089204) in SERPINB5-correlated promoter showed a significant association with an increased HCC risk (AOR?=?1.450; P?=?0.031). Haplotypes "T-C-A" and "C-C-C" (rs2289519?+?rs2289520?+?rs1455555) located in the SERPINB5 coding region had a decreased (AOR?=?0.744; P?=?0.031) and increased (AOR?=?1.981; P?=?0.001) HCC risk, respectively. Finally, an additional integrated in silico analysis confirmed that these SNPs affected SERPINB5 expression and protein stability, which significantly correlated with tumour expression and subsequently with tumour development and aggressiveness. Taken together, our findings regarding these biomarkers provide a prediction model for risk assessment.
| S-EPMC4879545 | biostudies-literature
Project description:Ovalbumin family contains three proteins with high sequence similarity: ovalbumin, ovalbumin-related protein Y (OVAY), and ovalbumin-related protein X (OVAX). Ovalbumin is the major egg white protein with still undefined function, whereas the biological activity of OVAX and OVAY has not yet been explored. Similar to ovalbumin and OVAY, OVAX belongs to the ovalbumin serine protease inhibitor family (ov-serpin). We show that OVAX is specifically expressed by the magnum tissue, which is responsible for egg white formation. OVAX is also the main heparin-binding protein of egg white. This glycoprotein with a predicted reactive site at Lys(367)-His(368) is not able to inhibit trypsin, plasmin, or cathepsin G with or without heparin as a cofactor. Secondary structure of OVAX is similar to that of ovalbumin, but the three-dimensional model of OVAX reveals the presence of a cluster of exposed positive charges, which potentially explains the affinity of this ov-serpin for heparin, as opposed to ovalbumin. Interestingly, OVAX, unlike ovalbumin, displays antibacterial activities against both Listeria monocytogenes and Salmonella enterica sv. Enteritidis. These properties partly involve heparin-binding site(s) of the molecule as the presence of heparin reverses its anti-Salmonella but not its anti-Listeria potential. Altogether, these results suggest that OVAX and ovalbumin, although highly similar in sequence, have peculiar sequential and/or structural features that are likely to impact their respective biological functions.
| S-EPMC3682532 | biostudies-literature
Project description:Cleavage of ovalbumin and angiotensinogen at sites homologous to the reactive centre loop of alpha 1-antitrypsin is not accompanied by the increase in heat-stability associated with the transition from the native stressed (S) structure to a cleaved relaxed (R) form that is typical of other serpins. Failure to undergo the S-R change in ovalbumin is not due to phosphorylation of Ser-344 near the sites of cleavage on the loop. The suggested explanation is the unique presence of bulky side chains at the P10-P12 site in ovalbumin and angiotensinogen.
| S-EPMC1133235 | biostudies-other
Project description:BackgroundThe human genome contains 13 clade B serpin genes at two loci, 6p25 and 18q21. The three genes at 6p25 all conform to a 7-exon gene structure with conserved intron positioning and phasing, however, at 18q21 there are two 7-exon genes and eight genes with an additional exon yielding an 8-exon structure. Currently, it is not known how these two loci evolved, nor which gene structure arose first--did the 8-exon genes gain an exon, or did the 7-exon genes lose one? Here we use the genomes of diverse vertebrate species to plot the emergence of clade B serpin genes and to identify the point at which the two genomic structures arose.ResultsAnalysis of the chicken genome indicated the presence of a single clade B serpin gene locus, containing orthologues of both human loci and both genomic structures. The frog genome and the genomes of three fish species presented progressively simpler loci, although only the 7-exon structure could be identified. The Serpinb12 gene contains seven exons in the frog genome, but eight exons in chickens and humans, indicating that the additional exon evolved in this gene.ConclusionWe propose a new model for clade B serpin evolution from a single 7-exon gene (either Serpinb1 or Serpinb6). An additional exon was gained in the Serpinb12 gene between the tetrapoda and amniota radiations to produce the 8-exon structure. Both structures were then duplicated at a single locus until a chromosomal breakage occurred at some point along the mammalian lineage resulting in the two modern loci.
| S-EPMC1308813 | biostudies-literature