Regulatory roles of LINE-1-encoded reverse transcriptase in cancer onset and progression

Ilaria Sciamanna _, Alberto Gualtieri, Pier Vincenzo Piazza and Corrado Spadafora

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Oncotarget. 2014; 5:8039-8051. https://doi.org/10.18632/oncotarget.2504

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Ilaria Sciamanna1, Alberto Gualtieri1, Pier Vincenzo Piazza2, Corrado Spadafora1

1Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy

2NeuroCentre Magendie, INSERM U862, Univ Bdx2, Bordeaux, France

Correspondence to:

Corrado Spadafora, e-mail: [email protected]

Keywords: Retrotransposon, reverse transcriptase, inhibitor, non coding RNA, cancer therapy

Received: August 01, 2014     Accepted: September 16, 2014     Published: October 29, 2014


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 RNA:DNA 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

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