Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

MEG3 (maternally expressed 3)

Identity

Other namesFLJ31163
FLJ42589
FP504
GTL2
PRO0518
PRO2160
prebp1
HGNC (Hugo) MEG3
LocusID (NCBI) 55384
Location 14q32.2
Location_base_pair Starts at 101292445 and ends at 101327360 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Genes flanking MEG3, in centromere to telomere direction on 14q32.2, are:
- DLK1 14q32.2 Delta-like 1 homolog (Drosophila)
- MEG3 14q32.2 Maternally Expressed Gene 3
- RTL1 14q32.31 Retrotransposon-like 1

DNA/RNA

Note The MEG3 gene is a maternally expressed imprinted gene. It forms the MEG3/DLK1 imprinted locus on 14q32, which contains multiple paternally or maternally imprinted genes, microRNAs and small nucleolar RNAs.
Description The MEG3 gene spans a region of 34,906 bp and consists of 10 exons.
Transcription Multiple transcripts are generated from the MEG3 gene due to alternative RNA splicing. The most prominent MEG3 transcript form is approximately 1.6 k nucleotides long and consists of exons 1, 2, 3, 4, 8, 9 and 10. This transcript is also known as the MEG3 transcript variant 1 (GenBank NR_002766).

Protein

Note MEG3 transcripts are non-coding RNAs (ncRNAs), which do not encode any functional proteins.
Expression MEG3 ncRNAs are highly expressed in brain, pituitary, placenta and adrenal gland; moderately in pancreas, ovary and testis; low in liver, prostate, spleen and mammary gland.
Function MEG3 does not encode any functional proteins. It acts as an RNA. The folding of MEG3 RNA plays an important role in its function. MEG3 ncRNAs have been shown to inhibit proliferation of several human tumor cell lines in culture. Transient expression of MEG3 activates p53 and induces the p53-dependent expression of its target gene GDF15. However, MEG3 can inhibit cell proliferation in the absence of p53.

Implicated in

Entity Clinically non-functioning pituitary adenomas
Disease Human pituitary adenomas arise from the anterior lobe of the pituitary, which contains hormone-secreting cells including somatotrophs (producing growth hormone), lactotrophs (prolactin), corticotrophs (adrenocorticotropic hormone), thyrotrophs (thyroid stimulating hormone) and gonadotrophs (follicle-stimulating hormone and luteinizing hormone). Clinically non-functioning pituitary adenomas usually show evidence of production of intact glycoprotein hormones and their free alpha and beta subunits yet typically do not secrete excessive hormones associated with a clinical syndrome. They are mostly derived from gonadotrophs. These tumors may grow large and cause considerable morbidity due to compression of adjacent normal structures.
Oncogenesis Expression of the MEG3 gene is lost in virtually all clinically non-functioning tumors of gonadotroph origin, but readily detectable in hormone-secreting clinically functioning tumors. The lack of MEG3 expression is most likely due to hypermethylation in the MEG3 gene promoter and in a region, called IG-DMR, which regulates imprinting of the MEG3 gene.
  
Entity Other human cancers
Oncogenesis MEG3 expression is lost in many human cancer cell lines. They include breast cancer lines MCF7 and T47D; bladder cancer lines T24 and 5637; prostate cancer line Du145; lung cancer line H1299; colon cancer lines HT29 and HT116; brain cancer lines H4, Kelly, SK-N-AS, SK-N-DZ and SK-N-F1. MEG3 expression is affected in 25% of primary neuroblastoma tumors.
  

External links

Nomenclature
HGNC (Hugo)MEG3   14575
Cards
AtlasMEG3ID44393ch14q32
Entrez_Gene (NCBI)MEG3  55384  maternally expressed 3 (non-protein coding)
GeneCards (Weizmann)MEG3
Ensembl (Hinxton)ENSG00000214548 [Gene_View]  chr14:101292445-101327360 [Contig_View]  MEG3 [Vega]
ICGC DataPortalENSG00000214548
cBioPortalMEG3
AceView (NCBI)MEG3
Genatlas (Paris)MEG3
WikiGenes55384
SOURCE (Princeton)
Genomic and cartography
GoldenPath (UCSC)MEG3  -  14q32.2   chr14:101292445-101327360 +  14q32.2   [Description]    (hg19-Feb_2009)
EnsemblMEG3 - 14q32.2 [CytoView]
Mapping of homologs : NCBIMEG3 [Mapview]
OMIM605636   
Gene and transcription
Genbank (Entrez)AB032607 AF052114 AJ413186 AJ413187 AK055725
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)AC_000146 NC_000014 NC_018925 NG_016853 NT_026437 NW_001838115 NW_004929393
Consensus coding sequences : CCDS (NCBI)MEG3
Cluster EST : UnigeneHs.654863 [ NCBI ]
CGAP (NCI)Hs.654863
Alternative Splicing : Fast-db (Paris)GSHG0045814
Alternative Splicing GalleryENSG00000214548
Gene ExpressionMEG3 [ NCBI-GEO ]     MEG3 [ SEEK ]   MEG3 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UI56 (Uniprot)
NextProtQ9UI56  [Medical]
With graphics : InterProQ9UI56
Splice isoforms : SwissVarQ9UI56 (Swissvar)
Related proteins : CluSTrQ9UI56
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
DMDM Disease mutations55384
Blocks (Seattle)Q9UI56
Human Protein AtlasENSG00000214548 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ9UI56
IPIIPI00006049   IPI00384148   
Protein Interaction databases
DIP (DOE-UCLA)Q9UI56
IntAct (EBI)Q9UI56
FunCoupENSG00000214548
BioGRIDMEG3
InParanoidQ9UI56
Interologous Interaction database Q9UI56
IntegromeDBMEG3
STRING (EMBL)MEG3
Ontologies - Pathways
Ontology : AmiGO
Ontology : EGO-EBI
Protein Interaction DatabaseMEG3
Wikipedia pathwaysMEG3
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)MEG3
snp3D : Map Gene to Disease55384
SNP (GeneSNP Utah)MEG3
SNP : HGBaseMEG3
Genetic variants : HAPMAPMEG3
Exome VariantMEG3
1000_GenomesMEG3 
ICGC programENSG00000214548 
Mutations and Diseases : HGMDMEG3
Mutations and Diseases : intOGenMEG3
Genomic VariantsMEG3  MEG3 [DGVbeta]
dbVarMEG3
ClinVarMEG3
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM605636   
MedgenMEG3
GENETestsMEG3
Disease Genetic AssociationMEG3
Huge Navigator MEG3 [HugePedia]  MEG3 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneMEG3
Homology/Alignments : Family Browser (UCSC)MEG3
Phylogenetic Trees/Animal Genes : TreeFamMEG3
Chemical/Protein Interactions : CTD55384
Chemical/Pharm GKB GenePA30737
Clinical trialMEG3
Cancer Resource (Charite)ENSG00000214548
Other databases
Probes
Litterature
PubMed39 Pubmed reference(s) in Entrez
CoreMineMEG3
iHOPMEG3
OncoSearchMEG3

Bibliography

The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA.
Schuster-Gossler K, Bilinski P, Sado T, Ferguson-Smith A, Gossler A.
Dev Dyn. 1998 Jun;212(2):214-28.
PMID 9626496
 
Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q.
Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F.
Genes Cells. 2000 Mar;5(3):211-20.
PMID 10759892
 
Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12.
Lin SP, Youngson N, Takada S, Seitz H, Reik W, Paulsen M, Cavaille J, Ferguson-Smith AC.
Nat Genet. 2003 Sep;35(1):97-102.
PMID 12937418
 
A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells.
Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A.
J Clin Endocrinol Metab. 2003 Nov;88(11):5119-26.
PMID 14602737
 
Epigenetic alteration at the DLK1-GTL2 imprinted domain in human neoplasia: analysis of neuroblastoma, phaeochromocytoma and Wilms' tumour.
Astuti D, Latif F, Wagner K, Gentle D, Cooper WN, Catchpoole D, Grundy R, Ferguson-Smith AC, Maher ER.
Br J Cancer. 2005 Apr 25;92(8):1574-80.
PMID 15798773
 
Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors.
Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A.
J Clin Endocrinol Metab. 2005 Apr;90(4):2179-86.
PMID 15644399
 
High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12.
Tierling S, Dalbert S, Schoppenhorst S, Tsai CE, Oliger S, Ferguson-Smith AC, Paulsen M, Walter J.
Genomics. 2006 Feb;87(2):225-35.
PMID 16309881
 
Activation of p53 by MEG3 non-coding RNA.
Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A.
J Biol Chem. 2007 Aug 24;282(34):24731-42.
PMID 17569660
 
Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas.
Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, Stratakis CA, Hedley-Whyte ET, Klibanski A.
J Clin Endocrinol Metab. 2008 Oct;93(10):4119-25.
PMID 18628527
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written11-2008Yunli Zhou
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA

Citation

This paper should be referenced as such :
Zhou, Y
MEG3 (maternally expressed 3)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(10):726-727.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/MEG3ID44393ch14q32.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Aug 26 15:28:37 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.