%0 Journal Article
%A Tristán-Ramos, Pablo
%A Rubio-Roldan, Alejandro
%A Peris, Guillermo
%A Sánchez, Laura
%A Amador-Cubero, Suyapa
%A Viollet, Sebastien
%A Cristofari, Gael
%A Heras, Sara R.
%T The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition
%D 2020
%U http://hdl.handle.net/10668/3782
%X Nearly 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.
%K Lung neoplasms
%K Carcinoma, squamous cell
%K Genes, tumor suppressor
%K MicroRNAs
%K Neoplasias pulmonares
%K Carcinoma de células escamosas
%K Genes Supresores de Tumor
%K MicroARNs
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