Binding Protein Gene Research Articles

Identification and validation of seven RNA binding protein genes as a prognostic signature in oral cavity squamous cell carcinoma

ABSTRACT RNA binding proteins (RBPs) play a pivotal role in various biological processes, and aberrant expression of RBPs is closely associated with tumorigenesis and progression. However, the role of RBPs in oral cavity squamous cell carcinoma (OCSCC) is yet unveiled. In this study, RNA sequences and clinical information of OCSCC samples were acquired from The Cancer Genome Atlas (TCGA) database. A total of 650 RBPs, with significantly different expression between healthy and OCSCC samples, were identified using the limma package. A prognostic model was constructed by Lasso-Cox analysis, resulting in the determination of 7 prognosis-related RBPs: ERMP1, RNASE3, ARL4D, CSRP2, ULK1, ZC3H12D, and RPS28. Based on the prognostic model, the risk scores of the OCSCC samples were calculated. The capability of the prognostic model was further evaluated using the receiver operating characteristic curve (ROC). The areas under ROC were 0.764, 0.771, and 0.809 at 1, 3 and 5-year respectively in the TCGA dataset. Internal and external validation showed satisfactory predictive capability for prognosis in OCSCC. In addition, a nomogram was created to graphically present the model. To further validate the analytical data, qRT-PCR was performed on normal and OCSCC cell lines. The mRNA expression of the 7 prognostic genes was in accordance with the analytical results. Functional analysis and gene connection networks were used to describe the biological functions and underlying interactions among the 7 prognostic genes Overall, 7 prognosis-related RBPs were identified, which could be used to predict clinical prognosis and to identify potential therapeutic targets for OCSCC.

Investigating TBP CAG/CAA trinucleotide repeat expansions in a Taiwanese cohort with ALS

Intermediate-length CAG repeats in ATXN2 have been well recognized as a genetic risk factor for amyotrophic lateral sclerosis (ALS). However, the role of similar trinucleotide repeat expansions in the TATA-box binding protein gene (TBP), another disease-associated gene for inherited ataxia, in ALS remains elusive. To assess the association between TBP trinucleotide repeat expansions and ALS, we investigated the repeat lengths in 325 unrelated ALS patients and 1500 controls in the Taiwanese population. The most common size of repeats in the patients and controls were both 36. The repeat lengths ranged from 29 to 46 repeats in the ALS patients and 27 to 43 repeats in the controls. Two ALS patients carried a TBP allele with a repeat number equal or greater than 44 (44 and 46). The patient with the 46 trinucleotide repeats also had a C9ORF72 GGGGCC hexanucleotide repeat expansion. The odds ratio of an individual carrying the CAG/CAA repeats ≥ 44 to have ALS is 23.2 (95% confidence interval: 1.11–484.24; p = 0.04). Our findings suggest that intermediate-length CAG/CAA repeat expansions in TBP may associate with ALS risk.

Functional Analysis of Odorant-Binding Proteins 12 and 17 from Wheat Blossom Midge Sitodiplosis mosellana Géhin (Diptera: Cecidomyiidae)

Simple SummarySitodiplosis mosellana is one of the most destructive pests of wheat. Adults rely highly on wheat spike volatiles to search and locate oviposition sites. Insect odorant-binding proteins (OBPs) are important in binding and transporting host plant volatiles to the olfactory receptors. Therefore, OBP-based behavioral interference is believed to be a novel and effective pest management strategy. The objectives of this study were to clone two S. mosellana female antenna-enriched OBP genes (SmosOBP12 and SmosOBP17), determine the functions of the encoded SmosOBP proteins in binding wheat volatiles, and investigate behavioral responses of female S. mosellana to odorant molecules. Results indicated that SmosOBP12 had a broader ligand-binding spectrum than SmosOBP17 to wheat volatiles. Female S. mosellana showed intensive response to 3-hexanol, 1-octen-3-ol, D-panthenol, 3-carene, (Z)-3-hexenylacetate, hexyl acetate, methyl salicylate, heptyl acetate, ethyl heptanoate, α-farnesene, and ocimene. Notably, all these compounds except α-farnesene exhibited strong affinity to SmosOBP12. In conclusion, SmosOBP12 may play more crucial roles than SmosOBP17 in perception and transportation of biologically active host volatiles. This information has enhanced our molecular understanding of the S. mosellana olfaction, which could also serve as an important reference for developing attractants or repellents to control this pest.The wheat blossom midge Sitodiplosis mosellana, one of the most disastrous wheat pests, depends highly on olfactory cues to track suitable plants. To better understand the olfactory recognition mechanisms involved in host selection, in the present study we cloned two S. mosellana adult antenna-specific odorant binding protein (OBP) genes, SmosOBP12 and SmosOBP17, and evaluated bacterially expressed recombinant proteins for their selectivity and sensitivity for host wheat volatiles using the fluorescence-based ligand binding assay. The results showed that both SmosOBPs effectively bound alcohol, ester, ketone, and terpenoid compounds. Particularly, SmosOBP12 had significantly higher affinities (Ki < 10.5 μM) than SmosOBP17 (Ki2 > 0.1 μM) to 3-hexanol, 1-octen-3-ol, D-panthenol, 3-carene, (Z)-3-hexenylacetate, hexyl acetate, methyl salicylate, heptyl acetate, and ethyl heptanoate. Consistently, S. mosellana females were attracted to all these chemicals in a behavioral assay using Y-tube olfactometer. SmosOBP12 also bound aldehyde, but neither bound alkanes. Notably, SmosOBP12 exhibited strong affinity to ocimene (Ki = 8.2 μM) that repelled S. mosellana. SmosOBP17, however, was insensitive to this compound. Taken together, our results indicate that SmosOBP12 may play a greater role than SmosOBP17 in perceiving these biologically active plant volatiles.

A new fungus-mediated RNAi method established and used to study the fatty acid and retinol binding protein function of the plant-parasitic nematode Aphelenchoides besseyi

ABSTRACT RNA interference (RNAi) is a powerful tool for gene functional analysis of plant-parasitic nematodes (PPNs). RNAi involving soaking in a dsRNA solution and in planta methods is commonly applied in the study of gene function in PPNs. However, certain problems restrict the application of these methods. Therefore, more convenient and effective RNAi methods need to be established for different PPNs according to their biological characteristics. In this study, the fatty acid and retinoid binding protein genes (Ab-far-1, Ab-far-4, and combinatorial Ab-far-1 and Ab-far-4) of the rice white tip nematode (RWTN), Aphelenchoides besseyi, were used as target genes to construct a fungal RNAi vector, and the Ab-far-n dsRNA transgenic Botrytis cinerea (ARTBn) were generated using Agrobacterium-mediated transformation technology. After RWTN feeding on ARTBn, the expression of Ab-far-1 and Ab-far-4 in the nematodes was efficiently silenced, and the reproduction and pathogenicity of the nematodes were clearly inhibited. The Ab-far-1 and Ab-far-4 co-RNAi effects were better than the effects when each gene was individually targeted with RNAi. Additionally, the RNAi induced when RWTNs fed on ARTB1 were persistent and heritable. Thus, a new method of fungus-mediated RNAi was established for fungivorous PPNs and was verified as effective and applicable to the study of nematode gene function. This technique will remove the technological bottlenecks and provide a new method to studying the multiple genes with polygene co-RNAi in fungivorous PPNs. This study also provides a theoretical basis and new thought for further study of the gene function in PPNs. Abbreviations: FAR(Fatty acid and retinol-binding proteins); RWTN (The rice white tip nematode, Aphelenchoides besseyi); Ab-far-n (Fatty acid and retinol binding protein gene of A. besseyi); ARTB1 (Ab-far-1 hpRNA transgenic Botrytis cinerea); ARTB4 (Ab-far-4 hpRNA transgenic Botrytis cinerea); ARTB1/4 (combinatorial Ab-far-1 and Ab-far-4 hpRNA transgenic B. cinerea); EVTB (Empty vector transgenic B. cinerea); GRTB (eGFP hpRNA transgenic B. cinerea); WTB (Wild-type B. cinerea).

Antibiotic analysis and whole genome sequencing of two nocardia farcinica strains causing joint infection

Objective: To analyze the molecular characteristics and antibiotic susceptibility of two strains of Nocardia farcinica isolated from patients with joint infection using whole genome sequencing. Methods: Two strains of Nocardia farcinica causing knee-joint infections in two elderly patients were collected in January 2020. Whole genome sequencing was used to determine the nocardia species. Drug sensitivity test was performed using the micro-broth dilution and E-test method according to CLSI M24 guideline. ABRicate was used to analyze drug resistance and virulence genes. Snippy and other bioinformatic tools were used for genomic comparison, and to construct SNP homologous tree. Results: The clinical isolates in this study were both Nocardia farcinica. Antimicrobial susceptibility test showed the isolates were resistant to ceftriaxone, cefepime, cefotaxime and trimethoprim/sulfamethoxazole (TMP/SMX). Imipenem, linezolid and amoxicillin-clavulanic acid showed good activity. Four antibiotic resistance genes including class A β-lactamase gene far-1, RNA polymerase binding protein gene RbpA, multi-drug resistance efflux pump transcription activator gene MtrA and regulatory transcription factor gene vanR-O were identified in the Nocardia farcinica genomes, which conferred resistance to beta-lactams, rifampicin, macrolides and vancomycin respectively. No acquired TMP/SMX resistance genes were identified. There are multiple missense mutations in the dihydrofolate reductase family genes. Four virulence genes of icl, mbtH, phoP, and relA that are homologous to Mycobacterium tuberculosis were found. SNP homologous tree analysis showed the two Nocardia strains were closely related, and there were only ten SNP sites, six compound substitutions and one deletion mutation between them. Conclusions: Whole genome sequencing technology is helpful to explore the molecular characteristics and resistance mechanisms of Nocardia species. Nocardia farcinica has a trend of spreading in China. Resistance to TMP/SMX is worthy of attention. The mutation of genes involved in the metabolic pathway of dihydrofolate might be one of multiple TMP/SMX resistance mechanisms.

Synergistic Effect of Omega-3 Fatty Acids and Oral-Hypoglycemic Drug on Lipid Normalization through Modulation of Hepatic Gene Expression in High Fat Diet with Low Streptozotocin-Induced Diabetic Rats.

Type 2 diabetes mellitus, which an outcome of impaired insulin action and its secretion, is concomitantly associated with lipid abnormalities. The study was designed to evaluate the combinational effect of omega-3 fatty acids (flax and fish oil) and glibenclamide on abnormal lipid profiles, increased blood glucose, and impaired liver and kidney functions in a high fat diet with low streptozotocin (STZ)-induced diabetic rats, including its probable mechanism of action. The male Wistar rats (n = 48) were distributed into eight groups. All animal groups except the healthy received a high fat diet (HFD) for 90 days. Further, diabetes was developed by low dose STZ (35 mg/kg). Diabetic animals received, omega-3 fatty acids (500 mg/kg), along with glibenclamide (0.25 mg/kg). Both flax and fish oil intervention decreased (p ≤ 0.001) serum triglycerides and very low density lipoprotein and elevated (p ≤ 0.001) high density lipoprotein levels in diabetic rats. Total cholesterol and low-density lipoprotein level was decreased (p ≤ 0.001) in fish oil-treated rats. However, it remained unaffected in the flax oil treatment group. Both flax and fish oil intervention downregulate the expression of fatty acid metabolism genes, transcription factors (sterol regulatory element-binding proteins-1c and nuclear factor-κβ), and their regulatory genes i.e., acetyl-coA carboxylase alpha, fatty acid synthase, and tumor necrosis factors-α. The peroxisome proliferator-activated receptor gamma gene expression was upregulated (p ≤ 0.001) in the fish oil treatment group. Whereas, carnitine palmitoyltransferase 1 and fatty acid binding protein gene expression were upregulated (p ≤ 0.001) in both flax and fish oil intervention group.

Influence of vitamin D binding protein polymorphism, demographics and lifestyle factors on vitamin D status of healthy Malaysian pregnant women

BackgroundVitamin D deficiency (VDD) has been related to vitamin D binding protein (GC) gene polymorphism, demographics and lifestyle factors in different populations. However, previous studies only focused on demographic and lifestyle factors or genetic factors alone. Therefore, this cross-sectional study aimed to assess the association between GC gene polymorphism, demographics and lifestyle factors with VDD among Malaysian pregnant women.MethodInformation on demographic characteristics, dietary vitamin D intake from supplement and food, time spent outdoors, skin type and clothing were collected using a questionnaire. Plasma total 25-hydroxyvitamin D (25OHD) levels were measured using an Ultra-High-Performance Liquid Chromatography (UHPLC). Maternal GC single nucleotide polymorphisms (SNPs) (rs4588 and rs7041) were determined using restriction fragment length polymorphism (RFLP) technique.ResultsResults showed that 50.2% of pregnant women were vitamin D deficient (25OHD < 30 nmol/L). VDD (25OHD < 30 nmol/L) was significantly associated with age, veiled clothing, maternal vitamin D intakes from both food and supplements, and GC rs7041(and GC diplotypes). In contrast to previous studies that reported for non-pregnant population, a significant positive association was found between CC genotype for SNP GC rs7041, GC 1s–1s and GC If-2 with risk of VDD (25OHD < 30 nmol/L).ConclusionsThe high prevalence of maternal VDD found in this study suggests the need for urgent development and implementation of vitamin D supplementation or fortification strategies to reduce VDD among pregnant women. The discrepancy in the association between GC rs7041 gene polymorphism and VDD reflects the variation in the factors associated with VDD in pregnancy compared to non-pregnant state.

Serum vitamin D, vitamin D receptor and binding protein genes polymorphisms in restless legs syndrome.

Several studies showed lower serum 25-hydroxyvitamin D levels in patients with idiopathic restless legs syndrome (RLS) compared with matched controls, and a single study showed an association between the rs731236 single nucleotide polymorphism (SNP) in the vitamin D receptor (VDR) gene and the risk for RLS. We aimed to study the relationship between the serum 25-hydroxyvitamin D levels and to confirm previous findings related to SNPs in the VDR and the GC vitamin D binding protein (GC) gene, with the risk for RLS in the Spanish Caucasian population. We genotyped 285 idiopathic RLS patients and 325 age and sex-matched controls for VDRrs2228750, VDRrs7975232, VDRrs739837, VDRrs78783628, GCrs7041 and GCrs4588 SNPs using TaqMan assays, and determined serum 25-hydroxyvitamin D levels in 111 idiopathic RLS patients and 167 controls using an ELISA commercial kit. Serum 25-hydroxyvitamin D levels were significantly higher in RLS patients than in controls but were unrelated with the 7 SNPs studied. None of the 7 SNPs analyzed was associated with the risk for idiopathic RLS or with a positive family history of RLS. However, RLS patients carrying the rs7975232CC genotype or the rs7975232C allele, had a higher frequency of response to GABAergic drugs. Associations between the age at onset and the severity of RLS with SNPs were inconsistent. This study shows an association between increased serum concentrations of 25-hydroxyvitamin D and a lack of association between 7 SNPs in the VDR and in the GC genes with RLS in the Spanish Caucasian population.

Association of vitamin D deficiency with vitamin D binding protein (DBP) and CYP2R1 polymorphisms in Iranian population

BackgroundMicronutrients are crucial for the promotion of human's well-being via the biological processes. Vitamin D is one of the most important ones with its vital role in calcium homeostasis in our body. Vitamin D deficiencies would definitely bring about various skeletal and non-skeletal disorders. In this study we have assessed the influence of two single-nucleotide polymorphisms (SNPs) of GC gene (vitamin D binding protein gene), and one of the CYP2R1 (Vitamin D 25-Hydroxylase enzyme), on vitamin D deficiency and insufficiency. Methods196 healthy adults' Iranian population (the real Persian race living in Fars province) cases were participated in this study, dividing into three groups of: normal, deficient and insufficient, considering their vitamin D concentration. The blood specimen was obtained and DNA was extracted from leukocytes. Following this, restricted fragment length polymerase chain reaction (RFLP-PCR) was used for genotyping throughout the processes and two SNPs of DBP (vitamin D binding protein), rs4588 and rs7041, and one of CYP2R1, rs10741657, were assessed. Meanwhile, we have evaluated the serum levels of 25-Hydroxy vitamin D3 with ELISA method. ResultsThe results showed no significant differences between three aforementioned groups in terms of seven various nature-nurture factors. Between three SNPs which were genotyped and assessed, rs7041 was the one that have drawn a significant distinction between groups. Its GT and TT genotypes were remarkably higher in insufficient and deficient groups respectively. Moreover, four haplotypes of rs4588 and rs7041 were evaluated and CT and AT ones illustrated a dramatic frequency rates in deficient and insufficient groups in turn. Neither of the remaining haplotypes (CG, AG) revealed significant frequencies among the groups though. ConclusionWe have concluded that both DBP and CYP2R1 SNPs could be effective for the regulation of vitamin D levels, however rs7041 and its genotypes was by far the most effective ones in vitamin D deficiencies.

Association of rs7041 and rs4588 polymorphisms of vitamin D binding protein gene in pulmonary tuberculosis

Vitamin D deficiency is often associated with tuberculosis susceptibility. Variants of vitamin D binding protein gene are reported to be associated with blood circulating concentration of 25(OH)D levels. The aim of the present study was to understand the association of rs7041 (G/T) and rs4588 (C/A) polymorphisms with tuberculosis susceptibility/protection in 125 Healthy controls (HCs) and 125 pulmonary tuberculosis (PTB) patients and to understand whether the gene variants have any influence on 25(OH)D levels in South Indian population. The genotyping for both the polymorphisms were done by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) method. 25(OH)D levels were estimated by ELISA method. The results revealed that under codominant model, rs4588 ‘CA' genotype significantly associated with TB susceptibility [OR: 1.47 (0.85–2.55); p = 0.049] and associated with 47.4% 25(OH)D deficiency in PTB patients. Whereas, under recessive model (‘AA' vs ‘CC' + ‘CA') rs4588 ‘AA' genotype significantly associated with TB protection [OR: 0.14 (0.02–1.29); p = 0.042]. Whereas in rs7041 polymorphism, under overdominant model (‘TG' vs ‘GG+’TT'), no association was found. Increased 25(OH)D levels were found with rs7041 “GG”, and rs4588 “CC” genotype in HCs and PTB patients. Haplotypes ‘TA' and ‘TC' associated with susceptibility to TB in males compared with females [‘TA' - OR: 4.18 (1.84–9.49); ‘TC' - OR: 3.63 (1.34–9.84)]. The results suggest that the heterozygous genotype rs4588 “CA” significantly associated with susceptibility while rs4588 “AA” genotype significantly associated with TB protection. Gene variants with 25(OH)D deficiency revealed no significant association due to limited sample size. However, in rs7041 “TG” and rs4588 “CA” genotype was associated with 61.1% and 47.4% 25(OH)D deficiency (OR > 2.0) in PTB patients. Future studies with larger sample size are needed to confirm this study finding.

Cancer frequency among the patients with myotonic dystrophy in the South Korean population using the national health insurance database

Cancer frequency among the patients with myotonic dystrophy in the South Korean population using the national health insurance database

Relationship between rs2282679 gene locus polymorphism and vitamin D deficiency in college students

To investigate the relationship between vitamin D binding protein gene rs2282679 A/C polymorphism with blood vitamin D levels. A total of 286 eligible subjects were selected from one university in Hebei Province. Serum 25-hydroxylated vitamin D levels were measured by liquid chromatography-mass spectrometry, and gene chip was used for genotyping of rs2282679 locus. Statistical analysis was performed using R software. A total of 285 participants in the study completed the experiment, and result indicated that the distribution of the rs2282679 locus A/C polymorphism in the participants was consistent with the Hardy-Weinberg equilibrium. The genotype of rs2282679 was significantly associated with serum vitamin D insufficiency and deficiency(P=0. 031). Allele A was a risk factor for vitamin D insufficiency and deficiency. The OR value of allele C relative to A was 0. 65, and the genetic pattern of allele C relative to A was dominant(P=0. 03). The vitamin D-binding protein gene rs2282679 was significantly associated with serum vitamin D insufficiency and deficiency in college students, and A-allele is a risk factor accounting for vitamin D insufficiency and deficiency in college students.

Effects of Phosphoethanolamine Supplementation on Mitochondrial Activity and Lipogenesis in a Caffeine Ingestion Caenorhabditis elegans Model.

Caffeine intake is strongly linked to lipid metabolism. We previously reported the age-dependent physiological effects of caffeine intake in a Caenorhabditis elegans model. Since nutritional status can actively influence metabolism and overall health, in this study, we evaluated the effect of caffeine intake on lipid metabolism in adult-stage C. elegans. We found that, in C. elegans, fat storage and the level of phosphoethanolamine (PE) were significantly reduced with caffeine intake. In addition, mitochondrial activity decreased and mitochondrial morphology was disrupted, and the expression of oxidative stress response genes, hsp-6, gst-4, and daf-16, was induced by caffeine intake. Furthermore, the level of an energy metabolism sensor, phospho-AMP-activated protein kinase, was increased, whereas the expression of the sterol regulatory element binding protein gene and its target stearoyl-CoA desaturase genes, fat-5, -6, and -7, was decreased with caffeine intake. These findings suggest that caffeine intake causes mitochondrial dysfunction and reduces lipogenesis. Interestingly, these changes induced by caffeine intake were partially alleviated by PE supplementation, suggesting that the reduction in mitochondrial activity and lipogenesis is in part because of the low PE level, and proper dietary supplementation can improve organelle integrity.

Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases.

Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half-life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genetic variants in the VDBP gene in correlation with certain diseases, mostly concerning cancers (breast, prostate, pancreatic, lung, colorectal, basal cell carcinoma cancer and cutaneous melanoma) or other related diseases (thyroid autoimmunity disorders, obesity, diabetes mellitus, bone metabolism, rheumatoid arthritis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, tuberculosis and coronary artery diseases).

Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale.

Collagen family genes and related genes might be associated with prognosis of patients with gastric cancer: an integrated bioinformatics analysis and experimental validation.

BackgroundGastric cancer (GC) is disease with a high morbidity. The purpose of this study was to identify genes essential to GC development in patients and to reveal the underlying mechanisms of progression.MethodsBioinformatics analysis is an effective tool for discovering essential genes of different disease states. We used the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs), the DAVID online tool to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs, the STRING database to construct the protein-protein interaction (PPI) network of DEGs, the Oncomine and the Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) databases to analyze the gene expression differences, the Human pan-Cancer Methylation database (MethHC) to compare the DNA methylation of genes, and the Kaplan-Meier plotter to show the survival analysis of DEGs. We performed Real-Time quantitative PCR (RT-qPCR) experiment to confirm our analysis results.ResultsAfter the integration of four Gene Expression Series (GSEs), we identified 407 DEGs. GO and KEGG pathway analysis indicated that the upregulated DEGs were significantly enriched in Extracellular Matrix (ECM) related functions and pathways. The main DEGs were collagens (COLs). Moreover, the downregulated DEGs were enriched in ethanol oxidation. Several groups of DEGs, such as insulin-like growth factor binding protein (IGFBP), collagen (COL) and serpin peptidase inhibitors (SERPIN) gene families, constituted several PPI networks. In the Oncomine database, all of the collagen genes were highly expressed in breast cancer, esophageal cancer, GC, head and neck cancer and pancreatic cancer, compared with normal tissues. Consistently, from the TCGA-STAD database, most of the collagens (COLs) were highly expressed and exhibited methylated variation in GC patients. In GC patients, some of these collagen (COL) genes related to worse prognosis, as evidenced by the results from the Kaplan-Meier plotter database analysis. Our RT-qPCR results showed that collagen type III α1 chain (COL3A1) was highly expressed in GC cells. Collagen type V α1 chain (COL5A1) was highly expressed, except in AGS cells, which was consistent with our analysis.ConclusionsCollagen (COL) family genes might serve as progression and prognosis markers of GC.

The influenza virus NS1A binding protein gene modulates macrophages response to cytokines and phagocytic potential in inflammation

Macrophages show remarkable phenotypic plasticity in response to environmental signals. Although it is generally less considered, cytoskeletal changes in macrophages influence their phenotype, including phagocytosis and secretion of soluble cytokines. Influenza virus NS1A-binding protein (Ivns1abp) belongs to the Kelch family of proteins that play a central role in actin cytoskeleton dynamics by directly associating with F-actin and by protecting against actin derangement. Due to its role in cytoskeleton preservation, the Ivns1abp gene might be a critical regulator of the macrophage phenotype and function under inflammatory conditions. In this study, we determine that the modulation of the Ivns1abp gene in macrophages could modify resistance to macrophages against inflammation and maintain functional phagocytosis. Our results indicate that inflammatory insults inhibit the Ivns1abp gene, whereby phagocytosis is inhibited and the ability of macrophages to induce proliferation and repair of damaged cells is compromised. Furthermore, our results show that inflammatory insults alter the activity of the transcription factor c-myc, a factor which directly modulates the expression of the Ivns1abp gene. In conclusion, this study demonstrates a central role of lvns1abp in promoting and preserving a reparative macrophage phenotype and resistance to this inflammatory environment.

Genetic variants of vitamin D metabolism-related DHCR7/NADSYN1 locus and CYP2R1 gene are associated with clinical features of Parkinson’s disease

Purpose/aim of the study Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Vitamin D deficiency is suggested to be related to PD. A genome-wide association study indicated that genes involved in vitamin D metabolism affect vitamin D levels. Among these genes, single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP/GC) genes have also been demonstrated to be associated with PD risk. Our aim was to investigate the relevance of SNPs within the 7-dehydrocholesterol reductase/nicotinamide adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) locus and vitamin D 25-hydroxylase (CYP2R1) gene, which encode important enzymes that play a role in the vitamin D synthesis pathway, with PD and its clinical features. Materials and methods Genotypes of 382 PD patients and 240 cognitively healthy individuals were evaluated by a LightSNiP assay for a total of 10 SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene. Results There were no significant differences in the allele and genotype distributions of any of the SNPs between any patient groups and healthy subjects. However, our results indicated that all of the SNPs within the DHCR7/NADSYN1 locus and CYP2R1 gene, except rs1993116, were associated with clinical motor features of PD including initial predominant symptom, freezing of gait (FoG) and falls as well as disease stage and duration of the disease. Conclusions In conclusion, genetic variants of the DHCR7/NADSYN1 locus and the CYP2R1 gene might be related to the inefficient utilization of vitamin D independent from vitamin D levels, and it might result in differences in the clinical features of PD patients.

Goldberg-Shprintzen syndrome is determined by the absence, or reduced expression levels, of KIFBP.

Goldberg–Shprintzen syndrome (GOSHS) is caused by loss of function variants in the kinesin binding protein gene (KIFBP). However, the phenotypic range of this syndrome is wide, indicating that other factors may play a role. To date, 37 patients with GOSHS have been reported. Here, we document nine new patients with variants in KIFBP: seven with nonsense variants and two with missense variants. To our knowledge, this is the first time that missense variants have been reported in GOSHS. We functionally investigated the effect of the variants identified, in an attempt to find a genotype–phenotype correlation. We also determined whether common Hirschsprung disease (HSCR)‐associated single nucleotide polymorphisms (SNPs), could explain the presence of HSCR in GOSHS. Our results showed that the missense variants led to reduced expression of KIFBP, while the truncating variants resulted in lack of protein. However, no correlation was found between the severity of GOSHS and the location of the variants. We were also unable to find a correlation between common HSCR‐associated SNPs, and HSCR development in GOSHS. In conclusion, we show that reduced, as well as lack of KIFBP expression can lead to GOSHS, and our results suggest that a threshold expression of KIFBP may modulate phenotypic variability of the disease.

Development and validation of a RNA binding protein gene pair-associated prognostic signature for prediction of overall survival in hepatocellular carcinoma

BackgroundIncreasing evidence has demonstrated the correlation between hepatocellular carcinoma (HCC) prognosis and RNA binding proteins (RBPs) dysregulation. Thus, we aimed to develop and validate a reliable prognostic signature that can estimate the prognosis for HCC.MethodsGene expression profiling and clinical information of 374 HCC patients were derived from the TCGA data portal. The survival-related RBP pairs were determined using univariate cox-regression analysis and the signature was built based on LASSO analysis. All patients were divided patients into high-and low-risk groups according to the optimal cut off of the signature score determined by time-dependent receiver operating characteristic (ROC) curve analysis. The predictive value of the signature was further validated in an independent cohort.ResultsA 37-RBP pairs signature consisting of 61 unique genes was constructed which was significantly associated with the survival. The RBP-related signature accurately predicted the prognosis of HCC patients, and patients in high-risk groups showed poor survival in two cohorts. The novel signature was an independent prognostic factor of HCC in two cohorts (all P < 0.001). Furthermore, the C-index of the prognostic model was 0.799, which was higher than that of many established risk models. Pathway and process enrichment analysis showed that the 61 unique genes were mainly enriched in translation, ncRNA metabolic process, RNA splicing, RNA modification, and translational termination.ConclusionThe novel proposed RBP-related signature based on relative expression orderings could serve as a promising independent prognostic biomarker for patients with HCC, and could improve the individualized survival prediction in HCC.