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MEG3 noncoding RNA: a tumor suppressor

2012· review· en· 729 citations· W2099176640 on OpenAlex· 10.1530/jme-12-0008

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Abstract

Maternally expressed gene 3 (MEG3) is an imprinted gene belonging to the imprinted DLK1-MEG3 locus located at chromosome 14q32.3 in humans. Its mouse ortholog, Meg3, also known as gene trap locus 2 (Gtl2), is located at distal chromosome 12. The MEG3 gene encodes a long noncoding RNA (lncRNA) and is expressed in many normal tissues. MEG3 gene expression is lost in an expanding list of primary human tumors and tumor cell lines. Multiple mechanisms contribute to the loss of MEG3 expression in tumors, including gene deletion, promoter hypermethylation, and hypermethylation of the intergenic differentially methylated region. Re-expression of MEG3 inhibits tumor cell proliferation in culture and colony formation in soft agar. This growth inhibition is partly the result of apoptosis induced by MEG3. MEG3 induces accumulation of p53 (TP53) protein, stimulates transcription from a p53-dependent promoter, and selectively regulates p53 target gene expression. Maternal deletion of the Meg3 gene in mice results in skeletal muscle defects and perinatal death. Inactivation of Meg3 leads to a significant increase in expression of angiogenesis-promoting genes and microvessel formation in the brain. These lines of evidence strongly suggest that MEG3 functions as a novel lncRNA tumor suppressor.

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The record

Venue
Journal of Molecular Endocrinology
Topic
RNA modifications and cancer
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthJarislowsky Foundation
Keywords
MEG3BiologyGeneGenomic imprintingGene expressionLocus (genetics)Regulation of gene expressionMolecular biologyDNA methylationTumor suppressor geneLong non-coding RNACancer researchRNAGeneticsCarcinogenesis
Has abstract in OpenAlex
yes