MEG3 (maternally expressed 3)

2008-11-01   Yunli Zhou 

Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

Identity

HGNC
LOCATION
14q32.2
LOCUSID
ALIAS
FP504,GTL2,LINC00023,NCRNA00023,PRO0518,PRO2160,onco-lncRNA-83,prebp1
FUSION GENES

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).

Proteins

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 name
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 name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
157987732005Epigenetic alteration at the DLK1-GTL2 imprinted domain in human neoplasia: analysis of neuroblastoma, phaeochromocytoma and Wilms' tumour.Astuti D et al
186285272008Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas.Gejman R et al
129374182003Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12.Lin SP et al
107598922000Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q.Miyoshi N et al
96264961998The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA.Schuster-Gossler K et al
163098812006High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12.Tierling S et al
146027372003A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells.Zhang X et al
156443992005Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors.Zhao J et al
175696602007Activation of p53 by MEG3 non-coding RNA.Zhou Y et al

Other Information

Locus ID:

NCBI: 55384
MIM: 605636
HGNC: 14575
Ensembl: ENSG00000214548

Variants:

dbSNP: 55384
ClinVar: 55384
TCGA: ENSG00000214548
COSMIC: MEG3

RNA/Proteins

Expression (GTEx)

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PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD
PA165817398MyelosuppressionDiseaseClinicalAnnotationassociatedPD
PA166122058mucositisDiseaseClinicalAnnotationassociatedPD
PA166122986radiotherapyChemicalClinicalAnnotationassociatedPD
PA443340AnemiaDiseaseClinicalAnnotationassociatedPD
PA443875DermatitisDiseaseClinicalAnnotationassociatedPD
PA444773LeukopeniaDiseaseClinicalAnnotationassociatedPD
PA445113NeutropeniaDiseaseClinicalAnnotationassociatedPD
PA445846ThrombocytopeniaDiseaseClinicalAnnotationassociatedPD

References

Pubmed IDYearTitleCitations
196567762009DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific.337
175696602007Activation of p53 by MEG3 non-coding RNA.231
216252152011microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer.231
262057902015MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures.174
240989112013Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression.143
146027372003A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells.132
222347982012Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation.127
107598922000Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q.117
200320572010Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions.113
199668052010The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes.112

Citation

Yunli Zhou

MEG3 (maternally expressed 3)

Atlas Genet Cytogenet Oncol Haematol. 2008-11-01

Online version: http://atlasgeneticsoncology.org/gene/44393/meg3