| Identity |
| Other names | FLJ31163 |
| 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 |
| 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 articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 11-2008 | Yunli 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. November 2008 . URL : http://AtlasGeneticsOncology.org/Genes/MEG3ID44393ch14q32.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/2042/44582/1/11-2008-MEG3ID44393ch14q32.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed May 1 13:08:00 CEST 2013 |
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