MEG3 (maternally expressed 3)

2008-11-01   Yunli Zhou  

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

Identity

HGNC
MEG3
LOCATION
14q32.2
LOCUSID
55384
ALIAS
FP504,GTL2,LINC00023,NCRNA00023,PRO0518,PRO2160,onco-lncRNA-83,prebp1
FUSION GENES
Show Gene Fusions

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.

Article 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)

0
100
200
300
400
500
600
700
800
900
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

PharmGKB

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

References

Pubmed IDYearTitleCitations
361289172024Changes in Serum LncRNA MEG3/miR-181b and UCH-L1 Levels in Patients with Moderate and Severe Intracerebral Hemorrhage.1
376886462024Altered expression of long noncoding RNA MEG3 in the offspring of gestational diabetes mellitus induces impaired glucose tolerance in adulthood.2
378243922024The ceRNA Mechanism of lncRNA MEG3/miR-21-5p/SPRY2 in Cell Proliferation and Apoptosis in Bladder Cancer.0
378653502024The lncRNA MEG3/miRNA-21/P38MAPK axis inhibits coxsackievirus 3 replication in acute viral myocarditis.0
380629692024[Long Noncoding RNAs MEG3, TUG1, and hsa-miR-21-3p Are Potential Diagnostic Biomarkers for Coronary Artery Disease].0
380724022024HGF facilitates methylation of MEG3, potentially implicated in vemurafenib resistance in melanoma.0
382363402024LncRNA MEG3 suppresses erastin-induced ferroptosis of chondrocytes via regulating miR-885-5p/SLC7A11 axis.3
382407012024Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1.1
382711372024Long noncoding RNA MEG3 regulates cell proliferation and apoptosis by disrupting microRNA-9-5p-mediated inhibition of NDRG1 in prostate cancer.0
382819452024m(6)A methylation-mediated regulation of LncRNA MEG3 suppresses ovarian cancer progression through miR-885-5p and the VASH1 pathway.2
383476322024Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study.0
383763442024RhoGDIβ inhibition via miR-200c/AUF1/SOX2/miR-137 axis contributed to lncRNA MEG3 downregulation-mediated malignant transformation of human bronchial epithelial cells.0
384525872024Harnessing the supremacy of MEG3 LncRNA to defeat gastrointestinal malignancies.2
385185162024Multifaceted roles of Meg3 in cellular senescence and atherosclerosis.1
386865832024MEG3 shuttled by exosomes released from human bone marrow mesenchymal stem cells promotes TP53 stability to regulate MCM5 transcription in keloid fibroblasts.0

Citation

Yunli Zhou

MEG3 (maternally expressed 3)

Atlas Genet Cytogenet Oncol Haematol. 2008-11-01

Online version: http://atlasgeneticsoncology.org/gene/44393/meg3-(maternally-expressed-3)