title: LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer?
abstract: Long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons are insertional mutagens capable of altering the genomic landscape in many ways. Activation of the normally silent LINE-1 retrotransposon is associated with a high level of cancer-associated DNA damage and genomic instability. Studies of LINE-1 have so far focused mainly on changes in gene expression, and our knowledge of its impact on functional non-coding RNAs is in its infancy. However, current evidence suggests that a significant number of human miRNAs originate from retrotransposon sequences. Furthermore, LINE-1 is generally not expressed in normal tissues while its expression is widespread in epithelial cancers. Based on our recent studies, we demonstrate a functional link between aberrant LINE-1 expression and deregulation of let-7 miRNA expression. Since the expression of let-7 is modulated by LINE-1 activity, we discuss possible mechanisms for this effect and how the silencing of LINE-1 activation could provide new therapeutic options for cancer treatment. Based on the deep sequencing of small RNAs in parallel with gene expression profiling in breast cancer cells, we have identified potential pathways linking L1 activity to let-7 processing and maturation and ultimately to the control of stemness in human cancer cells.
authors.affiliation: Department of Molecular Bioscience, John Curtin School of Medical Research, The Australian National University Canberra, ACT, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ohms
authors.affiliation: Department of Molecular Bioscience, John Curtin School of Medical Research, The Australian National University Canberra, ACT, Australia ; Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center Houston, TX, USA.
authors.forename: Sung-Hun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Molecular Bioscience, John Curtin School of Medical Research, The Australian National University Canberra, ACT, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Rangasamy
keywords: LINE-1; cancer; gene modulation; let-7 microRNA; long non-coding RNA; retrotransposon