title: Regulatory roles of LINE-1-encoded reverse transcriptase in  cancer onset and progression.
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.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sciamanna
authors.forename: Alberto
authors.initials: A
authors.lastname: Gualtieri
authors.forename: Pier Francesco
authors.initials: PF
authors.lastname: Piazza
authors.forename: Corrado
authors.initials: C
authors.lastname: Spadafora
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012194:RNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D018894:Reverse Transcriptase Inhibitors; D012194:RNA-Directed DNA Polymerase