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Fabry disease (FD) is a rare genetic condition caused by mutations in the GLA gene, located on the X chromosome in the RPL36-HNRNPH2 readthrough genomic region. This gene produces an enzyme called alpha-galactosidase A (α-Gal A). When the enzyme does not function properly due to the mutations, it causes harmful substances called globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) to build up in the body's lysosomes. This accumulation can damage the kidneys, heart, eyes, and nervous system. Recent studies have shown that the RPL36A-HNRNPH2 readthrough loci, which include RPL36A and HNRNPH2 genes, as well as the regulatory sequence known as the GLA-HNRNPH2 bidirectional promoter, may also play a role in FD. However, the involvement of enhancer RNAs (eRNAs) in FD is still poorly understood despite their known role in various diseases. To investigate this further, we studied an RPL36A enhancer called GH0XJ101390 and showed its genomic setting in the RPL36-HNRNPH2 readthrough region; the eRNA is rich in Homotypic Clusters of TFBSs (HCTs) type and hosts a CpG Island (CGI). To test the functional correlation further with GLA, RPL36A, and HNRNPH2, we used siRNAs to knock down GH0XJ101390 in human kidney embryonic cells 293T. The results showed a significant decrease in RPL36A and GLA expression and a non-significant decrease in HNRNPH2 expression. These findings could have important implications for understanding the regulatory mechanisms of GH0XJ101390 and its potential role in FD. A better understanding of these mechanisms may improve diagnostic and therapeutic methods for FD, which could ultimately benefit patients with this rare condition.
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Human mesenchymal stem cells (MSCs) are isolated from various adult and perinatal tissues. Although mesenchymal stem cells from multiple sources exhibit similar morphology and cell surface markers, they differ in their properties. In this study, we determined that the expression of integrin alpha 6 (ITGA6) and ITGA6 antisense RNA (ITGA6-AS1) correlates with the proliferation, cell size, and differentiation potential. The expression of ITGA6 was inversely correlated with ITGA6-AS1 in MSCs. The expression of ITGA6 was higher, but ITGA6-AS1 was lower in MSCs from cord placenta junction, cord tissue, and Wharton's jelly. In contrast, ITGA6 expression was lower, while ITGA6-AS1 was higher in MSCs from the placenta. The bioinformatic analysis showed that ITGA6 genomic DNA transcribes ITGA6-AS1 from the reverse strand, overlapping ITGA6 exon-2. Additionally, we identify several putative promoters (P1-P10) of ITGA6. ITGA6-P10 is CG rich and contains CGI. EMBOSS Cpgplot software revealed a CGI length of 180 bp that extends from nucleotide 125 to 304 of the P10 sequence. We suggest that the post-transcriptional regulation of the ITGA6 in mesenchymal stem cells is controlled by the ITGA6-AS1, which could be a critical factor responsible for the heterogeneity in function and cell fate of human MSCs. These results may provide further impetus for investigations to unravel the mechanisms of ITGA6 regulation that could help maintain or improve the properties of mesenchymal stem cells.
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Fabry disease (FD) is a rare inherited disease characterized by a wide range of symptoms attributed to GLA mutations resulting in defective α-galactosidase A (α-Gal A) and accumulation of glycosphingolipids. The GLA locus is paired in a divergent manner with the heterogeneous nuclear ribonucleoprotein HNRNPH2 locus mapped in the RPL36A-HNRNPH2 readthrough locus. As a follow-up to our recent finding of the co-regulation of GLA and HNRNPH2 via a bidirectional promoter (BDP) in normal kidney and skin cells, the potential accumulative influence of BDP methylation and GLA mutation on the severity of FD in patients from the same family, two males and two females carrying a GLA deletion mutation, c.1033_1034delTC (p.Ser345Argfs) was addressed in the present study. The molecular analyses of the FD patients compared with the control revealed that the expression of GLA was significantly low (P<0.05), and HNRNPH2 showed a tendency of low expression (P=0.1) when BDP methylation was elevated in FD patients, compared with low BDP methylation and high GLA expression (P<0.05), and a high trend of HNRNPH2 expression in normal individuals. The accumulative effects of the mutation and BDP methylation with the severity of the disease were observed in three patients. One male FD patient, a member of the FD family diagnosed with progressive loss of kidney function, hypertension, and eventually a stroke, and the lowest level of α-Gal A enzyme activity showed the highest BDP DNA methylation level. It is concluded that the DNA methylation of GLA-HNRNPH2 BDP may serve a role in diagnosing and treating FD.
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Congenital nephrotic syndrome (CNS) is an autosomal recessive disorder usually detected in the first 3 months of life when the syndromes effects manifest, including edema and a failure to gain weight. A baby boy was admitted to the Neonatal Intensive Care Unit for prematurity (35 weeks) with unremarkable maternal prenatal laboratory tests. The patient had persistent systemic hypertension, hypoproteinemia, hypoalbuminemia and nephrotic range proteinuria. CNS was diagnosed, and genetic testing showed a homozygous variant, c.3024A>G (AGA>AGG) in exon 22 of the nephrin locus. Bioinformatics analysis suggested the genetic condition was likely a result of malfunctional DNA binding sites of transcription factors FOXL1 and FOXC1.
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Background: The therapeutically important DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) is silenced by promoter methylation in human brain cancers. The co-players/regulators associated with this process and the subsequent progression of MGMT gene transcription beyond the non-coding exon 1 are unknown. As a follow-up to our recent finding of a predicted second promoter mapped proximal to the exon 2 [Int. J. Mol. Sci.2021, 22(5), 2492], we addressed its significance in MGMT transcription. Methods: RT-PCR, RT q-PCR, and nuclear run-on transcription assays were performed to compare and contrast the transcription rates of exon 1 and exon 2 of the MGMT gene in glioblastoma cells. Results: Bioinformatic characterization of the predicted MGMT exon 2 promoter showed several consensus TATA box and INR motifs and the absence of CpG islands in contrast to the established TATA-less, CpG-rich, and GAF-bindable exon 1 promoter. RT-PCR showed very weak MGMT-E1 expression in MGMT-proficient SF188 and T98G GBM cells, compared to active transcription of MGMT-E2. In the MGMT-deficient SNB-19 cells, the expression of both exons remained weak. The RT q-PCR revealed that MGMT-E2 and MGMT-E5 expression was about 80- to 175-fold higher than that of E1 in SF188 and T98G cells. Nuclear run-on transcription assays using bromo-uridine immunocapture followed by RT q-PCR confirmed the exceptionally lower and higher transcription rates for MGMT-E1 and MGMT-E2, respectively. Conclusions: The results provide the first evidence for transcriptional pausing at the promoter 1- and non-coding exon 1 junction of the human MGMT gene and its activation/elongation through the protein-coding exons 2 through 5, possibly mediated by a second promoter. The findings offer novel insight into the regulation of MGMT transcription in glioma and other cancer types.
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Neoplasias Encefálicas/metabolismo , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , Proteínas Supresoras de Tumor/genética , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Metilación de ADN , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Exones , Glioblastoma/genética , Humanos , Regiones Promotoras Genéticas , Proteínas Supresoras de Tumor/metabolismoRESUMEN
BACKGROUND: The molecular regulation of increased MGMT expression in human brain tumors, the associated regulatory elements, and linkages of these to its epigenetic silencing are not understood. Because the heightened expression or non-expression of MGMT plays a pivotal role in glioma therapeutics, we applied bioinformatics and experimental tools to identify the regulatory elements in the MGMT and neighboring EBF3 gene loci. RESULTS: Extensive genome database analyses showed that the MGMT genomic space was rich in and harbored many undescribed RNA regulatory sequences and recognition motifs. We extended the MGMT's exon-1 promoter to 2019 bp to include five overlapping alternate promoters. Consensus sequences in the revised promoter for (a) the transcriptional factors CTCF, NRF1/NRF2, GAF, (b) the genetic switch MYC/MAX/MAD, and (c) two well-defined p53 response elements in MGMT intron-1, were identified. A putative protein-coding or non-coding RNA sequence was located in the extended 3' UTR of the MGMT transcript. Eleven non-coding RNA loci coding for miRNAs, antisense RNA, and lncRNAs were identified in the MGMT-EBF3 region and six of these showed validated potential for curtailing the expression of both MGMT and EBF3 genes. ChIP analysis verified the binding site in MGMT promoter for CTCF which regulates the genomic methylation and chromatin looping. CTCF depletion by a pool of specific siRNA and shRNAs led to a significant attenuation of MGMT expression in human GBM cell lines. Computational analysis of the ChIP sequence data in ENCODE showed the presence of NRF1 in the MGMT promoter and this occurred only in MGMT-proficient cell lines. Further, an enforced NRF2 expression markedly augmented the MGMT mRNA and protein levels in glioma cells. CONCLUSIONS: We provide the first evidence for several new regulatory components in the MGMT gene locus which predict complex transcriptional and posttranscriptional controls with potential for new therapeutic avenues.
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Biomarcadores de Tumor/metabolismo , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Glioma/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Proteínas Supresoras de Tumor/metabolismo , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Factor de Unión a CCCTC/genética , Factor de Unión a CCCTC/metabolismo , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Genómica , Glioma/genética , Glioma/patología , Humanos , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor Nuclear 1 de Respiración/genética , Factor Nuclear 1 de Respiración/metabolismo , Regiones Promotoras Genéticas , ARN Interferente Pequeño/genética , ARN no Traducido/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
Fabry disease (FD) is a rare hereditary disorder characterized by a wide range of symptoms caused by a variety of mutations in the galactosidase α (GLA) gene. The heterogeneous nuclear ribonucleoprotein (HNRNPH2) gene is divergently paired with GLA on chromosome X and is thought to be implicated in FD. However, insufficient information is available on the regulatory mechanisms associated with the expression of HNRNPH2 and the GLA loci. Therefore, the current study performed bioinformatics analyses to assess the GLA and HNRNPH2 loci and investigate the regulatory mechanisms involved in the expression of each gene. The regulatory mechanisms underlying GLA and HNRNPH2 were revealed. The expression of each gene was associated with a bidirectional promoter (BDP) characterized by the absence of TATA box motifs and the presence of specific transcription factor binding sites (TFBSs) and a CpG Island (CGI). The nuclear run-on transcription assay confirmed the activity of BDP GLA and HNRNPH2 transcription in 293T. Methylation-specific PCR analysis demonstrated a statistically significant variation in the DNA methylation pattern of BDP in several cell lines, including human adult epidermal keratinocytes (AEKs), human renal glomerular endothelial cells, human renal epithelial cells and 293T cells. The highest observed significance was demonstrated in AEKs (P<0.05). The results of the chromatin-immunoprecipitation assay using 293T cells identified specific TFBS motifs for Yin Yang 1 and nuclear respiratory factor 1 transcription factors in BDPs. The National Center for Biotechnology Information-single nucleotide polymorphism database revealed pathogenic variants in the BDP sequence. Additionally, a previously reported variant associated with a severe heterozygous female case of GLA FD was mapped in BDP. The results of the present study suggested that the expression of the divergent paired loci, GLA and HNRNPH2, were controlled by BDP. Mutations in BDP may also serve a role in FD and may explain clinical disease diversity.
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Lipopolysaccharide (LPS), a potent endotoxin present in the outer membrane of Gram-negative bacteria, causes chronic immune responses associated with inflammation. In the present study, the association between LPS and the dysbiosis of Gram-negative bacteria in the gut microbiome was determined in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (T2DM-CKD; stages 4 and 5, not on dialysis) compared with healthy individuals. Microbiome diversity was analyzed in patients with T2DM-CKD and healthy controls by sequencing the hypervariable sub-regions of the 16S ribosomal RNA gene from stool samples. Serum samples were assayed by ELISA for LPS, C-reactive protein (CRP), tumor necrosis factor-α (TNFα), interleukin-6 (IL6) and endothelin-1. A total of four gut Gram-negative phyla (Bacteroidetes, Proteobacteria, Fusobacteria and Verrucomicrobia) were identified in the gut microbiome of the T2DM-CKD and control groups. Proteobacteria, Verrucomicrobia and Fusobacteria exhibited significantly increased relative abundance in patients with T2DM-CKD when compared with controls (P<0.05). The levels of serum LPS were significantly increased in patients with T2DM-CKD compared with controls (P<0.05). Elevated serum LPS was significantly correlated with increased levels of TNFα, IL6 and CRP. The dysbiosis of Gram-negative bacteria in the gut microbiome of patients with T2DM-CKD may contribute to the elevated serum levels of LPS and the consequential effects on the inflammatory biomarkers in these patients. The association between the dysbiosis of Gram-negative bacteria in the gut microbiome of patients with T2DM-CKD, increased LPS levels and the effects on inflammatory biomarkers may provide insight into potential diagnostic and therapeutic approaches in the treatment of T2DM-CKD.
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Autosomal Dominant Polycystic Kidney Disease (ADPKD) typically results from a mutation in the PKD1 and PKD2 genes, which code for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Mutations in these genes promote renal cystic dysplasia and are a significant cause of End-Stage Kidney Disease (ESKD). Polycystic kidney disease-3 (PKD3), another form of ADPKD, is caused by mutations in glucosidase II alpha subunit (GANAB) gene and present in mid- and late adulthood. We report a description of an ADPKD case in a 12-year-old female presented bilateral renal cysts in adolescence. Two mutations in two genes PKD1 and GANAB were identified by targeted capture and next-generation sequencing (NGS) on an Illumina sequencing system. The identified PKD1 mutation p.Pro61Leu: c.182C > T (CCC > CTC) a missense type of uncertain clinical significance. However, the identified PKD1 mutation can alter transcription factors motifs and consequently disturb the transcription process. The second mutation identified in GANAB locus, p.Arg61Ter: c.181C > T, a nonsense type, CGA > TGA. The mutation is unreported pathogenic variant can cause loss of the glucosidase II alpha subunit normal protein function. Both the patient father and paternal grandmother had a history of ADPKD but never were tested. This case is the first case of combine presentation on PKD1 and PKD3 in a pediatric patient with nephrolithiasis.
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Tobacco smoking is a research topic of high interest to the public health in Iraq. Although Iraq is a country with a high percentage of smokers, we noticed the dearth of adequate studies and programs to deal with this problem. The percentage of smokers exceed 30% of the population and smoking problem becomes a permanent habit in adults and young people. The problems associated with tobacco smoking behavior related to individuals' post-traumatic stress disorder following post-war conflicts, and the social and cultural environment. The health consequences of tobacco smoking can harm almost every organ in the body, and there are reports confirmed the tobacco smoking is a high-risk factor for lung cancer and other diseases. The relative risk of lung cancer increases with increasing duration and intensity of smoking. Also, smoking associated with bladder, prostate, and head and neck cancers, in addition to respiratory diseases. Intervention efforts should focus on reducing the prevalence of cigarette smoking, introduce effective treatments for cancer and quit smoking. In this perspective article, we present our viewpoint and three scenarios to deal with the problem of tobacco smoking in Iraq. We recommend introducing educational, health and legislative policies for quitting smoking and using effective treatments for cancer.
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Tobacco smoking is widespread behavior in Qatar and worldwide and is considered one of the major preventable causes of ill health and death. Nicotine is part of tobacco smoke that causes numerous health risks and is incredibly addictive; it binds to the α7 nicotinic acetylcholine receptor (α7nAChR) in the brain. Recent studies showed α7nAChR involvement in the initiation and addiction of smoking. Kynurenic acid (KA), a significant tryptophan metabolite, is an antagonist of α7nAChR. Inhibition of kynurenine 3-monooxygenase enzyme encoded by KMO enhances the KA levels. Modulating KMO gene expression could be a useful tactic for the treatment of tobacco initiation and dependence. Since KMO regulation is still poorly understood, we aimed to investigate the 5' and 3'-regulatory factors of KMO gene to advance our knowledge to modulate KMO gene expression. In this study, bioinformatics methods were used to identify the regulatory sequences associated with expression of KMO. The displayed differential expression of KMO mRNA in the same tissue and different tissues suggested the specific usage of the KMO multiple alternative promoters. Eleven KMO alternative promoters identified at 5'-regulatory region contain TATA-Box, lack CpG Island (CGI) and showed dinucleotide base-stacking energy values specific to transcription factor binding sites (TFBSs). The structural features of regulatory sequences can influence the transcription process and cell type-specific expression. The uncharacterized LOC105373233 locus coding for non-coding RNA (ncRNA) located on the reverse strand in a convergent manner at the 3'-side of KMO locus. The two genes likely expressed by a promoter that lacks TATA-Box harbor CGI and two TFBSs linked to the bidirectional transcription, the NRF1, and ZNF14 motifs. We identified two types of microRNA (miR) in the uncharacterized LOC105373233 ncRNA, which are like hsa-miR-5096 and hsa-miR-1285-3p and can target the miR recognition element (MRE) in the KMO mRNA. Pairwise sequence alignment identified 52 nucleotides sequence hosting MRE in the KMO 3' UTR untranslated region complementary to the ncRNA LOC105373233 sequence. We speculate that the identified miRs can modulate the KMO expression and together with alternative promoters at the 5'-regulatory region of KMO might contribute to the development of novel diagnostic and therapeutic algorithm for tobacco smoking.
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BACKGROUND: CYP1A1 gene polymorphisms and tobacco smoking are among several risk factors for various types of cancers, but their influence on breast cancer remains controversial. We analyzed the possible association of CYP1A1 gene polymorphisms and tobacco smoking-related breast cancer in women from Iraq. MATERIALS AND METHODS: In this case-control study, gene polymorphism of CYP1A1 gene (CYP1A1m1, T6235C and CYP1A1m2, A4889G) of 199 histologically verified breast cancer patients' and 160 cancer-free control women's specimens were performed by using PCR-based restriction fragment length polymorphism. RESULTS: Three genotype frequencies (TT, TC, and CC) of CYP1A1m1T/C appeared in 16.1, 29.6, and 54.3% of women with breast cancer, respectively, compared with 41.2, 40, and 18.8% in the control group, respectively. CYP1A1m1 CC genotype and C allele were significantly associated with increased risks for breast cancer in patients (54.3 and 69%, respectively) compared with controls (18.8 and 39%, respectively). While the three genotype frequencies (AA, AG, and GG) of CYP1A1m2A/G were detected in 20.1, 31.2, and 48.7% in patients compared with 46.3, 40.6, and 13.1% in controls, respectively. The frequency of GG genotypes and G allele was significantly higher in patients (48.7 and 64%, respectively) than in the controls (13.1 and 33%, respectively). Smoking women having either CC or GG genotypes showed a highly significant association with increased risk of breast cancer [odds ratio (OR) = 1.607, 95% confidence interval (CI) 0.91-1.64, p = 0.0001, and OR, 1.841, 95% CI, 0.88-1.67, p = 0.0001, respectively]. On the other hand, the T and A alleles of predominantly seen in healthy smoking women (83 and 85%, p = 0.0001, respectively). CONCLUSION: These findings indicated that both C and G alleles of CYP1A1m1 and m2 were significantly associated with elevated risk of breast cancer in Iraqi women, while the T and A alleles were predominantly seen in healthy controls which may indicate their protective role. The C and G association with breast cancer incidence was more prevalent among tobacco smoking patients. These polymorphisms may be used as biomarkers of breast cancer in women from Iraq.
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Cancer is a significant health problem in the Middle East and global population. It is well established that there is a direct link between tobacco smoking and cancer, which will continue to pose a significant threat to human health. The impact of long-term exposure to tobacco smoke on the risk of cancer encouraged the study of biomarkers for vulnerable individuals to tobacco smoking, especially children, who are more susceptible than adults to the action of environmental carcinogens. The carcinogens in tobacco smoke condensate induce DNA damage and play a significant role in determining the health and well-being of smokers, non-smoker, and primarily children. Cancer is a result of genomic and epigenomic malfunctions that lead to an initial premalignant condition. Although premalignancy genetic cascade is a much-delayed process, it will end with adverse health consequences. In addition to the DNA damage and mutations, tobacco smoke can cause changes in the DNA methylation and gene expression associated with cancer. The genetic events hint on the possible use of genomic-epigenomic changes in genes related to cancer, in predicting cancer risks associated with exposure to tobacco smoking. Bioinformatics provides indispensable tools to identify the cascade of expressed genes in active smokers and non-smokers and could assist the development of a framework to manage this cascade of events linked with the evolvement of disease including cancer. The aim of this mini review is to cognize the essential genomic processes and health risks associated with tobacco smoking and the implications of bioinformatics in cancer prediction, prevention, and intervention.
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Trimethylamine-N-oxide (TMAO) is a product of dietary, gut microbiome, and tissues metabolism. Elevated blood TMAO levels are associated with heart attack, stroke and chronic kidney disease (CKD). The purpose of our study was to investigate the gut microbiota associated with trimethylamine (TMA) production, the precursor of TMAO, and the serum levels of TMAO and inflammatory biomarkers associated with type 2 diabetes mellitus (T2DM) and CKD. Twenty adults with T2DM and advanced CKD and 20 healthy adults participated in the study. Analyses included anthropometric and metabolic parameters, characterization of TMA producing gut microbiota, and concentrations of TMAO, lipopolysaccharides (LPS) endotoxin, zonulin (Zo) gut permeability marker, and serum inflammatory and endothelial dysfunction biomarkers. Diversity of the gut microbiota was identified by amplification of V3-V4 regions of the 16S ribosomal RNA genes and DNA sequencing. TMAO was quantified by Mass Spectrometry and serum biomarkers by ELISA. The significance of measurements justified by statistical analysis. The gut microbiome in T2DM-CKD patients exhibited a higher incidence of TMA-producing bacteria than control, p < 0.05. The serum levels of TMAO in T2DM-CKD patients were significantly higher than controls, p < 0.05. TMAO showed a positive correlation with Zo and LPS, inflammatory and endothelial dysfunction biomarkers. A positive correlation was observed between Zo and LPS in T2DM-CKD subjects. An increased abundance of TMA-producing bacteria in the gut microbiota of T2DM-CKD patients together with excessive TMAO and increased gut permeability might impact their risk for cardiovascular disease through elevation of chronic inflammation and endothelial dysfunction.
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ß1,4-Galactosylransferases are a family of enzymes encoded by seven B4GALT genes and are involved in the development of anticancer drug resistance and metastasis. Among these genes, the B4GALT1 shows significant variations in the transcript origination sites in different cell types/tissues and encodes an interesting dually partitioning ß-1, 4-galactosyltransferase protein. We identified at 5'-end of B4GALT1 a 1.454 kb sequence forming a transcription regulatory region, referred to by us as the TR1-PE1, had all characteristics of a bidirectional promoter directing the transcription of B4GALT1 in a divergent manner along with its long non-coding RNA (lncRNA) antisense counterpart B4GALT1-AS1. The TR1-PE1 showed unique dinucleotide base-stacking energy values specific to transcription factor binding sites (TFBSs), INR and BRE, and harbored CpG Island (CGI) that showed GC skew with potential for R-loop formation at the transcription starting sites (TSSs). The 5'-regulatory axis of B4GALT1 also included five more novel TFBSs for CTCF, GLI1, TCF7L2, GATA3 and SOX5, in addition to unique (TG)18 repeats in conjunction with 22 nucleotide TG-associated sequence (TGAS). The five lncRNA B4GALT1-AS1 transcripts showed significant complementarity with B4GALT1 mRNA. In contrast, the rest of B4GALT genes showed fewer lncRNAs, and all lacked the (TG)18 and TGAS. Our results are strongly supported by the FANTOM5 study which showed tissue-specific variations in transcript origination sites for this gene. We suggest that the unique expression patterns for the B4GALT1 in normal and malignant tissues are controlled by a differential usage of 5'-B4GALT1 regulatory units along with a post-transcriptional regulation by the antisense RNA, which in turn govern the cell-matrix interactions, neoplastic progression, anticancer drug sensitivity, and could be utilized in personalized therapy.