MEG3 noncoding RNA: a tumor suppressor

By Yunli Zhou, Xun Zhang, A. Klibanski. Journal of Molecular Endocrinology, 2012

699 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d60eac1652735fbcea22bbfb161f2b7c8138d1bd

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Citations in the corpus

Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth (2014, background): “MEG3 exhibits a tumor suppressive function, and MEG3 mice show an increased expression of VEGFA in the brain.(21,22) Whether the deletion of MEG3 leads to an endothelial cell intrinsic angiogenesis defect is unclear.”
Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution (2015, background): “MEG3 is an imprinted lncRNA which is downregulated in many types of cancers and previously hypothesized to function as a tumor suppressor in a mechanism that is still not well understood [69-71].”
Long noncoding RNA in prostate, bladder, and kidney cancer. (2014, background): “This is demonstrated by the sequential assembly of PRNCR1 and PCGEM1with the AR [21], the structure of MEG3 imperative for its tumour suppressor functionality [53], or the multidomain organisation of steroid receptor RNA activator SRA [98].”
Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels (2019, background): “3 in human, is a tumor suppressor [95].”