MEG3

Summary

MEG3 (maternally expressed 3, HGNC:14575) is a long non-coding RNA gene on chromosome 14q32.2.

This gene is a maternally expressed imprinted gene. Multiple alternatively spliced transcript variants have been transcribed from this gene and all of them are long non-coding RNAs (lncRNAs). This gene is expressed in many normal tissues, but its expression is lost in multiple cancer cell lines of various tissue origins. It inhibits tumor cell proliferation in vitro. It also interacts with the tumor suppressor p53, and regulates p53 target gene expression. Its deletion enhances angiogenesis in vivo. Many experimental evidences demonstrate that this gene is a lncRNA tumor suppressor.

Source: NCBI Gene 55384 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14575
Approved symbol	MEG3
Name	maternally expressed 3
Location	14q32.2
Locus type	RNA, long non-coding
Status	Approved
Aliases	Lnc-DLK1-35, GTL2, NCRNA00023, LINC00023, onco-lncRNA-83
Ensembl gene	ENSG00000214548
Ensembl biotype	lncRNA
OMIM	605636
Entrez	55384
RNAcentral	URS0000759EA9 — lncRNA, 1595 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 72 — 72 lncRNA

ENST00000398460, ENST00000398461, ENST00000398474, ENST00000398518, ENST00000412736, ENST00000423456, ENST00000424076, ENST00000429159, ENST00000451743, ENST00000452120, ENST00000452514, ENST00000455286, ENST00000455531, ENST00000519709, ENST00000520714, ENST00000521256, ENST00000521404, ENST00000521812, ENST00000522618, ENST00000522771, ENST00000523671, ENST00000524035, ENST00000524131, ENST00000554639, ENST00000555928, ENST00000556407, ENST00000556736, ENST00000647780, ENST00000648123, ENST00000648138, ENST00000648456, ENST00000648512, ENST00000648547, ENST00000648609, ENST00000648802, ENST00000648820, ENST00000648950, ENST00000649036, ENST00000649086, ENST00000649161, ENST00000649174, ENST00000649261, ENST00000650023, ENST00000650041, ENST00000650077, ENST00000650513, ENST00000650549, ENST00000650556, ENST00000654077, ENST00000662362, ENST00000783967, ENST00000783968, ENST00000783969, ENST00000783970, ENST00000783971, ENST00000783972, ENST00000783973, ENST00000783974, ENST00000783975, ENST00000783976, ENST00000783977, ENST00000783978, ENST00000783979, ENST00000783980, ENST00000783981, ENST00000783982, ENST00000783983, ENST00000783984, ENST00000783985, ENST00000783986, ENST00000824814, ENST00000850894

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000398460 — 2 exons

Exon	Start	End
ENSE00001533234	100860749	100861018
ENSE00001533235	100857245	100860356

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 125.6018 / max 6406.0567, expressed in 960 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141506	120.4829	956
141533	1.8526	140
141531	1.8030	150
141532	0.4588	77
141518	0.2747	48
141516	0.2664	115
141517	0.1824	91
141507	0.1245	45
141512	0.1141	54
141519	0.0424	14

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	99.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.94	gold quality
cerebellar hemisphere	UBERON:0002245	99.93	gold quality
pituitary gland	UBERON:0000007	99.90	gold quality
cerebellar cortex	UBERON:0002129	99.84	gold quality
right adrenal gland	UBERON:0001233	99.82	gold quality
adrenal cortex	UBERON:0001235	99.81	gold quality
left adrenal gland	UBERON:0001234	99.80	gold quality
left adrenal gland cortex	UBERON:0035825	99.80	gold quality
right adrenal gland cortex	UBERON:0035827	99.80	gold quality
right frontal lobe	UBERON:0002810	99.79	gold quality
primary visual cortex	UBERON:0002436	99.72	gold quality
nucleus accumbens	UBERON:0001882	99.71	gold quality
left ovary	UBERON:0002119	99.69	gold quality
adrenal tissue	UBERON:0018303	99.67	gold quality
cerebellum	UBERON:0002037	99.66	gold quality
right ovary	UBERON:0002118	99.62	gold quality
lateral globus pallidus	UBERON:0002476	99.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.44	gold quality
amygdala	UBERON:0001876	99.43	gold quality
endocervix	UBERON:0000458	99.42	gold quality
middle temporal gyrus	UBERON:0002771	99.40	gold quality
putamen	UBERON:0001874	99.38	gold quality
occipital lobe	UBERON:0002021	99.37	gold quality
Ammon’s horn	UBERON:0001954	99.31	gold quality
caudate nucleus	UBERON:0001873	99.30	gold quality
substantia nigra pars compacta	UBERON:0001965	99.22	gold quality
cingulate cortex	UBERON:0003027	99.21	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	6395.29
E-HCAD-30	yes	6151.91
E-GEOD-180759	yes	2357.97
E-HCAD-35	yes	1835.30
E-MTAB-11268	yes	961.74
E-MTAB-10287	yes	113.59
E-CURD-119	yes	10.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CTCF, DNMT1, KLF4, TP53

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• MEG3 gene is imprinted, with preferential expression from the maternal allele. (PMID:10759892)
• MEG3 may represent a novel growth suppressor, which may play an important role in the development of human pituitary adenomas. (PMID:14602737)
• MEG3 may interact with the cAMP-dependent signaling pathway to be involved in the control of cell proliferation and other cAMP-related physiological functions. (PMID:16793321)
• MEG3 non-coding RNA may function as a tumor suppressor, whose action is mediated by both p53-dependent and p53-independent pathways (PMID:17569660)
• four patients with clinical features of upd(14)mat who show a maternal-only methylation pattern, but biparental inheritance for chromosome 14. (PMID:18454453)
• MEG3 is the first human gene identified expressed in multiple normal human pituitary cell types with loss of expression specifically restricted to clinically nonfunctioning pituitary adenomas. (PMID:18628527)
• MEG3 and SNRPN genes are abnormally methylated in AML and MDS patients, and methylation of MEG3, but not SNRPN, confers worse overall prognosis. (PMID:19595458)
• Data show that of IL10, LEP, ABCA1, GNASAS and MEG3 was higher among individuals who were periconceptionally exposed to the famine compared with their unexposed same-sex siblings. (PMID:19656776)
• designed allele-specific methylation study of the DLK1/GTL2 intergenic differentially methylated region allowed us to determine the parental origin of del(14q/IGH) in 9/20 analyzed cases. (PMID:19786834)
• Studies indicate the imprinted DLK1-MEG3 gene region of chromosome 14q32.2 contains a functional T1D candidate gene. (PMID:19966805)
• All MEG3 RNA isoforms contain three distinct secondary folding motifs M1, M2, and M3. Deletion analysis showed that motifs M2 and M3 are important for p53 activation (PMID:20032057)
• MEG3 inhibits colony formation in meningioma cells. MEG3 stimulates p53-mediated transactivation in these cell lines. Data are consistent with the hypothesis that MEG3 may be a tumor suppressor gene at chromosome 14q32 involved in meningioma progression. (PMID:20179190)
• intergenic differentially methylated region (IG-DMR) and the MEG3-DMR function as imprinting control centers in the placenta and the body (PMID:20585555)
• methylation-dependent tissue-specific regulation of the lncRNA MEG3 by miR-29a may contribute to hepatocellular cancer growth. (PMID:21625215)
• MEG3 expression was lost in 20 of 38 (53%) pituitary adenomas (PMID:21850407)
• The DLK1-MEG3 locus plays a tumor suppressor role in human nonfunctioning adenomas. (PMID:21871428)
• data suggest an important role of MEG3 in the molecular etiology of glioma and implicate the potential application of MEG3 in glioma therapy. (PMID:22234798)
• Dwnregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. (PMID:23295831)
• This review indicated that MEG3 may have a significant role as a novel long noncoding RNA tumour suppressor in meningiomas. (PMID:23307326)
• Paternal methylation aberrations at imprinting control regions of DLK1-GTL2, MEST (PEG1), and ZAC (PLAGL1) and global methylation levels are not associated with idiopathic recurrent spontaneous miscarriages. (PMID:23415968)
• These results identified an important role of MEG3 in the molecular etiology of cervical cancer (PMID:23790166)
• Our findings present that MEG3 downexpression can be identified as a poor prognostic biomarker in gastric cancer and regulate cell proliferation and apoptosis in vitro. (PMID:24006224)
• Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. (PMID:24098911)
• We found that, while embryonal rhabdomyosarcomas tumors consistently show LOI of the differentially methylated regions at the DLK1-GTL2 locus, alveolar rhabdomyosarcomas tumors have erasure of imprinting (EOI) at this locus. (PMID:24173021)
• Decreased MEG3 expression was associated with tongue squamous cell carcinoma. (PMID:24343426)
• These results support a role for microRNAs of DLK1-MEG3 cluster and their epigenetic control by DNA methylation in the pathogenesis of type 2 diabetes mellitus. (PMID:24374217)
• Down-regulation of MEG3 is associated with gastric cancer. (PMID:24515776)
• Data suggest that WT1-as, MEG3 and ANRIL could potentially be used as new primary myelofibrosis (PMF) diagnostic biomarkers with prognostic implications. (PMID:24707949)
• Data suggest that MEG3 is epigenetically silenced in epithelial ovarian cancer (EOC) due to promoter hypermethylation, which may contribute to the development of EOC. (PMID:24859196)
• P8 and MEG3 mRNA levels were significantly lower in nonfunctioning and corticotroph adenomas compared with normal pituitary. (PMID:25126861)
• The results indicate the occurrence of epimutation affecting the IG-DMR and the MEG3-DMR in the two cases, and imply that UPD(14)mat and related (epi)genetic aberrations constitute a rare but important underlying factor for Silver-Russell Syndrome (PMID:25351781)
• Study shows low levels of MEG3 in severe preeclamptic placentas and determines its role on trophoblast apoptosis and migration suggesting that low levels of lncRNA MEG3 might lead to aberrant conditions of the trophoblast cells. (PMID:25358633)
• Meg3 overexpression in insulinoma cells down-regulated the expression of the protooncogene c-met. (PMID:25565142)
• our study demonstrated that MEG3 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that MEG3 may be a potential diagnostic and prognostic target in patients with colorectal cancer. (PMID:25636452)
• Findings demonstrated the inhibitory effect of MEG3 in vivo and vitro and illuminated that MEG3 could be a potential biomarker for the survival of hepatocellular carcinoma (HCC) patients. Its expression seemed to be regulated by UHRF1 in HCC. (PMID:25641194)
• novel evidence for the biological and clinical significance of lncRNA MEG3 expression as a potential biomarker for identifying patients with multiple myeloma by targeting BMP4 transcription (PMID:25753650)
• Loss of MEG3 expression is associated with Cisplatin Resistance in Lung Adenocarcinoma. (PMID:25992654)
• Downregulation of Meg3 enhances cisplatin resistance of lung cancer cells through activation of the WNT/beta-catenin signaling pathway. (PMID:26059239)
• MEG3 levels are inversely associated with VEGF levels, suggesting that MEG3 may be involved in OA development through the regulation of angiogenesis (PMID:26090403)
• MEG3 modulates the activity of TGF-beta genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA-DNA triplex formation. (PMID:26205790)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.