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

// Ilaria Sciamanna 1 , Alberto Gualtieri 1 , Pier Vincenzo Piazza 2 , Corrado Spadafora 1 1 Istituto Superiore di Sanita, Viale Regina Elena 299, Rome, Italy 2 NeuroCentre Magendie, INSERM U862, Univ Bdx2, Bordeaux, France Correspondence to: Corrado Spadafora, e-mail: cspadaf@tin.it Keywords: Retrotransposon, reverse transcriptase, inhibitor, non coding RNA, cancer therapy Received: August 01, 2014      Accepted: September 16, 2014      Published: October 29, 2014 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 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