Regulatory roles of LINE-1-encoded reverse transcriptase in cancer onset and progression.
Oncotarget
; 5(18): 8039-51, 2014 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-25478632
ABSTRACT
LINE-1 retrotransposons encode the reverse transcriptase (RT) enzyme, required for their own mobility, the expression of which is inhibited in differentiated tissues while being active in tumors. Experimental evidence indicate that the inhibition of LINE-1-derived RT restores differentiation in cancer cells, inhibits tumor progression and yields globally reprogrammed transcription profiles. Newly emerging data suggest that LINE-1-encoded RT modulates the biogenesis of miRNAs, by governing the balance between the production of regulatory double-stranded RNAs and RNADNA hybrid molecules, with a direct impact on global gene expression. Abnormally high RT activity unbalances the transcriptome in cancer cells, while RT inhibition restores "normal" miRNA profiles and their regulatory networks. This RT-dependent mechanism can target the myriad of transcripts - both coding and non-coding, sense and antisense - in eukaryotic transcriptomes, with a profound impact on cell fates. LINE-1-encoded RT emerges therefore as a key regulator of a previously unrecognized mechanism in tumorigenesis.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
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DNA Polimerase Dirigida por RNA
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Elementos Nucleotídeos Longos e Dispersos
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Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2014
Tipo de documento:
Article