Human Gene Set: BRUECKNER_TARGETS_OF_MIRLET7A3_DN


Standard name BRUECKNER_TARGETS_OF_MIRLET7A3_DN
Systematic name M11825
Brief description Genes down-regulated in A549 cells (lung cancer) expressing MIRLET7A3 [GeneID=406883] microRNA off a plasmid vector.
Full description or abstract MicroRNAs (miRNAs) are small noncoding RNAs that repress their target mRNAs by complementary base pairing and induction of the RNA interference pathway. It has been shown that miRNA expression can be regulated by DNA methylation and it has been suggested that altered miRNA gene methylation might contribute to human tumorigenesis. In this study, we show that the human let-7a-3 gene on chromosome 22q13.31 is associated with a CpG island. Let-7a-3 belongs to the archetypal let-7 miRNA gene family and was found to be methylated by the DNA methyltransferases DNMT1 and DNMT3B. The gene was heavily methylated in normal human tissues but hypomethylated in some lung adenocarcinomas. Let-7a-3 hypomethylation facilitated epigenetic reactivation of the gene and elevated expression of let-7a-3 in a human lung cancer cell line resulted in enhanced tumor phenotypes and oncogenic changes in transcription profiles. Our results thus identify let-7a-3 as an epigenetically regulated miRNA gene with oncogenic function and suggest that aberrant miRNA gene methylation might contribute to the human cancer epigenome.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17308078   Authors: Brueckner B,Stresemann C,Kuner R,Mund C,Musch T,Meister M,Sültmann H,Lyko F
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 Human_RefSeq
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