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 and aggressiveness. In this study, we explore the TSG role of CYGB, its influence on the phenotype of cancerous cells under stress conditions and the clinical significance of CYGB expression and promoter methylation in non-small cell lung cancer (NSCLC). DNA methylation-dependent expression silencing of CYGB is demonstrated in both clinical samples and cell lines. CYGB promoter was more frequently methylated in lung adenocarcinomas (P = 1.4 × 10(-4)). Demethylation by 5'-azadeoxycytidine partially restored CYGB expression in cell lines. Interestingly, trichostatin A triggered upregulation of CYGB expression in cancer cell lines and downregulation in non-tumourigenic ones. CYGB mRNA expression in NSCLC surgical specimens correlated with that of HIF1α and VEGFa (P < 1 × 10(-4)). Overexpression of CYGB in cancer cell lines reduced cell migration, invasion and anchorage-independent growth. Moreover, CYGB impaired cell proliferation, but only in the lung adenocarcinoma cell line (H358). Upon hydrogen peroxide treatment, CYGB protected cell viability, migratory potential and anchorage independence by attenuating oxidative injury. In hypoxia, CYGB overexpression decreased cell viability, augmented migration and anchorage independence in a cell-type-specific manner. In conclusion, CYGB revealed TSG properties in normoxia but promoted tumourigenic potential of the cells exposed to stress, suggesting a bimodal function in lung tumourigenesis, depending on cell type and microenvironmental conditions.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Oleksiewicz U,Liloglou T,Tasopoulou KM,Daskoulidou N,Bryan J,Gosney JR,Field JK,Xinarianos Gdoi
10.1093/hmg/ddt174subject
Has Abstractpub_date
2013-08-15 00:00:00pages
3207-17issue
16eissn
0964-6906issn
1460-2083pii
ddt174journal_volume
22pub_type
杂志文章abstract::Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat in the first exon of the HD gene, which results in a toxic polyglutamine stretch within huntingtin, the protein it encodes. Understanding the normal function of this essential protein is vital to u...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl467
更新日期:2007-02-15 00:00:00
abstract::Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-gl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu586
更新日期:2015-03-15 00:00:00
abstract::Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv183
更新日期:2015-08-15 00:00:00
abstract::Mutations in the survival motor neuron (SMN1) gene lead to the neuromuscular disease spinal muscular atrophy (SMA). Although SMA is primarily considered as a motor neuron disease, the importance of muscle defects in its pathogenesis has not been fully examined. We use both primary cell culture and two different SMA mo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu142
更新日期:2014-08-15 00:00:00
abstract::With 46 subunits, human mitochondrial complex I is the largest enzyme of the oxidative phosphorylation system. We have studied the assembly of complex I in cultured human cells. This will provide essential information about the nature of complex I deficiencies and will enhance our understanding of mitochondrial diseas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh262
更新日期:2004-10-15 00:00:00
abstract::Wolfram syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and ne...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz212
更新日期:2019-11-15 00:00:00
abstract::The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD) is causally related to a short Eco RI fragment detected by probe p13E-11. This remnant fragment is the result of a deletion of an integral number of tandemly arrayed 3.3 kb repeat units (D4Z4) on 4q35. Despite intensive efforts, no transcrib...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.8.1207
更新日期:1998-08-01 00:00:00
abstract::Glutamine (Q) expansion diseases are a family of degenerative disorders caused by the lengthening of CAG triplet repeats present in the coding sequences of seemingly unrelated genes whose mutant proteins drive pathogenesis. Despite all the molecular evidence for the genetic basis of these diseases, how mutant poly-Q p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds246
更新日期:2012-10-01 00:00:00
abstract::We describe a detection principle for indirect fluorescence in situ hybridization (FISH) methods that with only one or two antibody layers dramatically improves FISH signal intensities. The method uses as a first layer an anti-hapten immunoglobulin [or (strept)avidin] conjugated to peroxidase. The quintessence of the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.4.529
更新日期:1995-04-01 00:00:00
abstract::Meta-analysis of genome-wide association studies has resulted in the identification of hundreds of genetic variants associated with growth and stature. Determining how these genetic variants influence growth is important, but most are non-coding, and there is little understanding of how these variants contribute to ad...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddw165
更新日期:2016-08-01 00:00:00
abstract::Acetazolamide responsive hereditary paroxysmal cerebellar ataxia (APCA) is a rare autosomal dominant disorder characterized by attacks of cerebellar ataxia and dysarthria with normal or near normal neurologic function between attacks. A genome-wide search using polymorphic di- and tri-nucleotide repeats was initiated ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.2.279
更新日期:1995-02-01 00:00:00
abstract::Williams syndrome (WS) is a neurodevelopmental disorder caused by a 1.5-1.8 Mbp deletion on chromosome 7q11.23, affecting the copy number of 26-28 genes. Phenotypes of WS include cardiovascular problems, craniofacial dysmorphology, deficits in visual-spatial cognition and a characteristic hypersocial personality. Ther...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz176
更新日期:2019-10-15 00:00:00
abstract::Mutations in S-phase cyclin A-associated protein in the endoplasmic reticulum (SCAPER) cause a recessively inherited multisystemic disorder whose main features are retinal degeneration and intellectual disability. SCAPER, originally identified as a cell cycle regulator, was also suggested to be a ciliary protein. Beca...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa113
更新日期:2020-08-03 00:00:00
abstract::Proteins and protein networks associated with cochlear pathogenesis in the Ames waltzer (av) mouse, a model for deafness in Usher syndrome 1F (USH1F), were identified. Cochlear protein from wild-type and av mice at postnatal day 30, a time point in which cochlear pathology is well established, was analyzed by quantita...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq025
更新日期:2010-04-15 00:00:00
abstract::Lipoprotein lipase (LPL) is a 448-amino-acid head-to-tail dimeric enzyme that hydrolyzes triglycerides within capillaries. LPL is secreted by parenchymal cells into the interstitial spaces; it then binds to GPIHBP1 (glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1) on the basolateral fa...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds127
更新日期:2012-07-01 00:00:00
abstract::Atopic (allergic) asthma is the most common disease of childhood and is strongly genetic in origin. Many genome-wide screens for asthma and its associated traits have now been carried out, and genetic linkage has been consistently identified in several regions. It is probable that these loci contain major genes influe...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/9.16.2359
更新日期:2000-10-01 00:00:00
abstract::Hypomorphic mutations of the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), characterized by microcephaly, chromosomal instability, radiosensitivity, immunodeficiency and high cancer predisposition. Over 90% of NBS patients are homozygous for the 657Delta5 mutation and are of Slavic origin; however, 1...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi482
更新日期:2006-03-01 00:00:00
abstract::A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.4.621
更新日期:1999-04-01 00:00:00
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
更新日期:1995-12-01 00:00:00
abstract::A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of ...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddi230
更新日期:2005-08-01 00:00:00
abstract::First- and second-generation sequencing technologies have led the way in revolutionizing the field of genomics and beyond, motivating an astonishing number of scientific advances, including enabling a more complete understanding of whole genome sequences and the information encoded therein, a more complete characteriz...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddq416
更新日期:2010-10-15 00:00:00
abstract::Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.5.669
更新日期:1997-05-01 00:00:00
abstract::Niemann-Pick type C disease (NP-C) is a progressive lysosomal lipid storage disease caused by mutations in the NPC1 and NPC2 genes. NPC1 is essential for transporting cholesterol and other lipids out of lysosomes, but little is known about the mechanisms that control its cellular abundance and localization. Here we sh...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw204
更新日期:2016-08-15 00:00:00
abstract::Presenilins 1 and 2 (PS1/2), causative molecules for familial Alzheimer's disease (FAD), are multipass transmembrane proteins localized predominantly in the endoplasmic reticulum (ER) and Golgi apparatus. Heteromeric protein complexes containing PS1/2 are thought to participate in several functions, including intramem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi195
更新日期:2005-07-01 00:00:00
abstract::The group of dominant non-dystrophic myotonias, comprising disorders characterized by clinically similar forms of myogenic muscle stiffness, is genetically inhomogeneous. Dominant myotonia congenita (Thomsen's disease) is linked to CLCN1, the gene encoding the major muscle chloride channel, localized on chromosome 7q3...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.8.1397
更新日期:1995-08-01 00:00:00
abstract::A 1.5 Mb duplication within 17p11.2 is the major mutation causing both autosomal dominant and sporadic Charcot-Marie-Tooth disease type 1A (CMT1A). An independent origin for the mutation in each family has been postulated. The proposed genetic mechanism causing the CMT1A duplication is unequal nonsister chromatid exch...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.12.2031
更新日期:1993-12-01 00:00:00
abstract::The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx211
更新日期:2017-09-01 00:00:00
abstract::Turner syndrome is a complex human disorder that generally associates a 45,X karyotype to a female phenotype presenting with gonadal dysgenesis, short stature and a number of characteristic somatic features. It has been hypothesized that this specific phenotype was the consequence of the haploinsufficiency of some X-l...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.9.1565
更新日期:1995-09-01 00:00:00
abstract::Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated wit...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddz161
更新日期:2019-10-01 00:00:00
abstract::Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by the expansion of a polyglutamine tract within the SCA1 product, ataxin-1. Previously, using transgenic mice, it was demonstrated that in order for a mutant allele of ataxin-1 to cause disease it must be transported to the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.1.25
更新日期:2001-01-01 00:00:00