Tristán-Ramos, PabloRubio-Roldan, AlejandroPeris, GuillermoSánchez, LauraAmador-Cubero, SuyapaViollet, SebastienCristofari, GaelHeras, Sara R.2022-07-122022-07-122020-11-11Tristán-Ramos P, Rubio-Roldan A, Peris G, Sánchez L, Amador-Cubero S, Viollet S, et al. The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition. Nat Commun. 2020 Nov 11;11(1):5712http://hdl.handle.net/10668/3782Nearly half of the human genome is made of transposable elements (TEs) whose activity continues to impact its structure and function. Among them, Long INterspersed Element class 1 (LINE-1 or L1) elements are the only autonomously active TEs in humans. L1s are expressed and mobilized in different cancers, generating mutagenic insertions that could affect tumor malignancy. Tumor suppressor microRNAs are ∼22nt RNAs that post-transcriptionally regulate oncogene expression and are frequently downregulated in cancer. Here we explore whether they also influence L1 mobilization. We show that downregulation of let-7 correlates with accumulation of L1 insertions in human lung cancer. Furthermore, we demonstrate that let-7 binds to the L1 mRNA and impairs the translation of the second L1-encoded protein, ORF2p, reducing its mobilization. Overall, our data reveals that let-7, one of the most relevant microRNAs, maintains somatic genome integrity by restricting L1 retrotransposition.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Lung neoplasmsCarcinoma, squamous cellGenes, tumor suppressorMicroRNAsNeoplasias pulmonaresCarcinoma de células escamosasGenes Supresores de TumorMicroARNsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::Untranslated Regions::3' Untranslated RegionsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung NeoplasmsMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding SitesMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous CellMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::EndonucleasesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, NeoplasticMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Recessive::Genes, Tumor SuppressorMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Repetitive Sequences, Nucleic Acid::Interspersed Repetitive Sequences::Retroelements::Long Interspersed Nucleotide ElementsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung NeoplasmsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Small Untranslated::MicroRNAsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Protein BiosynthesisMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase::RNA-Directed DNA PolymeraseMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, CulturedWhole Genome Sequencingresearch article33177501Acceso abierto10.1038/s41467-020-19430-42041-1723PMC7658363