Abstract:
:Several studies have shown that testis-specific gene antigen (TSGA10) could be considered as a cancer testis antigen (CTA), except for one study which has identified it as a tumor suppressor gene. In order to exert its function, TSGA10 interacts closely with hypoxia inducible factor (HIF-1α) and since this interaction is still not completely defined, the exact role of TSGA10 in angiogenesis and invasion is also under question. The current study was conducted to investigate the function of TSGA10 gene and evaluate its potential effects on tumor angiogenesis and invasion. To do so, TSGA10 vector was designed for a stable transfection in HeLa cells, and then clonal selection was applied. The efficiency of transfection and the role of TSGA10 in abovementioned targets were evaluated by real-time PCR, western blot, zymography and ELISA tests in both normoxia and hypoxia. Invasion, migration and angiogenesis were assessed. Three-dimensional model of TSGA10 protein was accurately built in which TSGA10 docked to 2 domains of HIF-1α. Increased expression of TSGA10 correlated with decreased HIF-1α transcriptional activity and inhibited angiogenesis and HeLa cells invasion in normoxia as well as hypoxia. Docking analysis indicated that binding affinity of TSGA10 with TAD-C (CBP) domain of HIF-1α would be stronger than that with PAS-B domain. Our findings showed that overexpression of TSGA10 would induce disruption of HIF-1α axis and exert potent inhibitory effects on tumor angiogenesis and metastasis. Therefore, TSGA10 could be considered as a potent therapeutic candidate, prognostic factor and a cancer management tool.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Mansouri K,Mostafie A,Rezazadeh D,Shahlaei M,Modarressi MHdoi
10.1093/hmg/ddv461subject
Has Abstractpub_date
2016-01-15 00:00:00pages
233-44issue
2eissn
0964-6906issn
1460-2083pii
ddv461journal_volume
25pub_type
杂志文章abstract::A recurrent t(9;22) (q22;q12) chromosome translocation has been described in extraskeletal myxoid chondrosarcoma (EMC). Fluorescent in situ hybridization experiments performed on one EMC tumour indicated that the chromosome 22 breakpoint occurred in the EWS gene. Northern blot analysis revealed an aberrant EWS transcr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.12.2219
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abstract::Huntington's disease (HD) is caused by an expansion of a poly glutamine (polyQ) stretch in the huntingtin protein (HTT) that is necessary to cause pathology and formation of HTT aggregates. Here we ask whether expanded polyQ is sufficient to cause pathology and aggregate formation. By addressing the sufficiency questi...
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journal_title:Human molecular genetics
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更新日期:1995-03-01 00:00:00
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journal_title:Human molecular genetics
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abstract::Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death are poorly understood, and consequently, there are no treatments available. Previous studies sugg...
journal_title:Human molecular genetics
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更新日期:2016-09-01 00:00:00
abstract::Immunoglobulin-like domain containing receptor 1 (ILDR1) is a poorly characterized gene that was first identified in lymphoma cells. Recently, ILDR1 has been found to be responsible for autosomal recessive hearing impairment DFNB42. Patients with ILDR1 mutations cause bilateral non-progressive moderate-to-profound sen...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2014-12-01 00:00:00
abstract::The cone photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Mutations in the channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophy. We investigated the gene expression profiles in mouse retina with CNG channel deficiency usin...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2013-10-01 00:00:00
abstract::Ataxia-telangiectasia (A-T) is a multisystem, cancer-predisposing genetic disorder caused by deficiency of the ATM protein. To dissect the A-T phenotype, we augmented specific features of the human disease by generating mouse strains that combine Atm deficiency with dysfunction of other proteins. Increasing oxidative ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi324
更新日期:2005-10-01 00:00:00
abstract::Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotid...
journal_title:Human molecular genetics
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更新日期:2014-02-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt518
更新日期:2014-03-01 00:00:00
abstract::Megf7/Lrp4 is a member of the functionally diverse low-density lipoprotein receptor gene family, a class of ancient and highly conserved cell surface receptors with broad functions in cargo transport and cellular signaling. To gain insight into the as yet unknown biological role of Megf7/Lrp4, we have disrupted the ge...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi381
更新日期:2005-11-15 00:00:00
abstract::Dysregulation of Fused in Sarcoma (FUS) gene expression is associated with fronto-temporal lobar degeneration (FTLD), and missense mutations in the FUS gene have been identified in patients affected by amyotrophic lateral sclerosis (ALS). However, molecular and cellular defects underlying FUS proteinopathy remain to b...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw310
更新日期:2016-12-01 00:00:00
abstract::An increased rate of de novo copy number variants (CNVs) has been found in schizophrenia (SZ), autism and developmental delay. An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We us...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2014-12-15 00:00:00
abstract::Colobomatous macrophthalmia with microcornea syndrome (MACOM, Online Mendelian Inheritance in Man (OMIM) 602499) is an autosomal dominantly inherited malformation of the eye, which is characterized by microcornea with increased axial length, coloboma of the iris and of the optic disc, and severe myopia. We performed w...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu744
更新日期:2015-04-15 00:00:00
abstract::Centronuclear myopathies (CNM) are a subtype of congenital myopathies (CM) characterized by skeletal muscle weakness and an increase in the number of central myonuclei. We have previously identified three CNM probands, two with associated dilated cardiomyopathy, carrying striated preferentially expressed gene (SPEG) m...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy068
更新日期:2018-05-01 00:00:00
abstract::α-Mannosidosis is a lysosomal storage disorder caused by mutations in the MAN2B1 gene. The clinical presentation of α-mannosidosis is variable, but typically includes mental retardation, skeletal abnormalities and immune deficiency. In order to understand the molecular aetiology of α-mannosidosis, we describe here the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr167
更新日期:2011-07-01 00:00:00
abstract::Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A gene at Xq22.1. To determine the nature and frequency of the molecular lesions causing the classical and milder variant Fabry phenotypes, and for precise carrier detection in Fabry families, the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.10.1795
更新日期:1994-10-01 00:00:00
abstract::Primary open-angle glaucoma (POAG) is a complex disease with unknown causes. However, in the past decade, POAG has been linked to six chromosomal regions, of which the gene MYOC encoding myocilin and the gene OPTN encoding optineurin have been identified to harbor causal mutations (disease-causing variants, DCV). POAG...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
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更新日期:2004-04-01 00:00:00
abstract::With progress in genome-wide association studies of depression, from identifying zero hits in ~16 000 individuals in 2013 to 223 hits in more than a million individuals in 2020, understanding the genetic architecture of this debilitating condition no longer appears to be an impossible task. The pressing question now i...
journal_title:Human molecular genetics
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abstract::Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as multiple sclerosis (MS). As a large proportion of expression quantitative trait loci (eQTLs) are...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
abstract::Most quantitative trait loci (QTL) studies have focused on detecting the genetic effects of individual QTLs. This study thoroughly dissected the genetic components of type 2 diabetic mice, including a search for epistatic interactions and multi-locus additive effects that result in variation in diabetes-related phenot...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2006-01-01 00:00:00
abstract::Metabolic control of phenylalanine concentrations in body fluids is essential for cognitive development and executive function. The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2018-05-15 00:00:00
abstract::Cytoglobin (CYGB) is frequently downregulated in many types of human malignancies, and its exogenous overexpression reduces proliferation of cancer cells. Despite its implied tumour suppressor (TSG) functions, its exact role in carcinogenesis remains unclear as CYGB upregulation is also associated with tumour hypoxia ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt174
更新日期:2013-08-15 00:00:00
abstract::In order to characterize the dynamics of CTG repeat instability in somatic and germline tissue from myotonic dystrophy (DM) males we have used small pool polymerase chain reaction (PCR) in a detailed quantitative analysis of repeat length variation. We demonstrate that the heterogeneous smear of CTG repeats observed i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.1.1
更新日期:1995-01-01 00:00:00
abstract::Biased segregation of mitochondrial DNA variants has been widely documented, but little was known about its molecular basis. We set out to test the hypothesis that altering the balance between mitochondrial fusion and fission could influence the segregation of mutant and wild-type mtDNA variants, because it would modi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp281
更新日期:2009-09-15 00:00:00
abstract::The genetic defect underlying myotonic dystrophy (DM) has been identified as the expansion of an unstable trinucleotide repeat sequence, and this discovery has led to new approaches to diagnosis and genetic counselling in families with the disorder. We report the genetic analysis of a consanguineous DM family in which...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:1993-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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journal_title:Human molecular genetics
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更新日期:2012-03-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddx061
更新日期:2017-05-01 00:00:00