Cargando…

LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer?

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. Studi...

Descripción completa

Detalles Bibliográficos
Autores principales: Ohms, Stephen, Lee, Sung-Hun, Rangasamy, Danny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188135/
https://www.ncbi.nlm.nih.gov/pubmed/25339972
http://dx.doi.org/10.3389/fgene.2014.00338
_version_ 1782338221817987072
author Ohms, Stephen
Lee, Sung-Hun
Rangasamy, Danny
author_facet Ohms, Stephen
Lee, Sung-Hun
Rangasamy, Danny
author_sort Ohms, Stephen
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4188135
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-41881352014-10-22 LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer? Ohms, Stephen Lee, Sung-Hun Rangasamy, Danny Front Genet Genetics 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. Frontiers Media S.A. 2014-10-07 /pmc/articles/PMC4188135/ /pubmed/25339972 http://dx.doi.org/10.3389/fgene.2014.00338 Text en Copyright © 2014 Ohms, Lee and Rangasamy. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Ohms, Stephen
Lee, Sung-Hun
Rangasamy, Danny
LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer?
title LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer?
title_full LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer?
title_fullStr LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer?
title_full_unstemmed LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer?
title_short LINE-1 retrotransposons and let-7 miRNA: partners in the pathogenesis of cancer?
title_sort line-1 retrotransposons and let-7 mirna: partners in the pathogenesis of cancer?
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188135/
https://www.ncbi.nlm.nih.gov/pubmed/25339972
http://dx.doi.org/10.3389/fgene.2014.00338
work_keys_str_mv AT ohmsstephen line1retrotransposonsandlet7mirnapartnersinthepathogenesisofcancer
AT leesunghun line1retrotransposonsandlet7mirnapartnersinthepathogenesisofcancer
AT rangasamydanny line1retrotransposonsandlet7mirnapartnersinthepathogenesisofcancer