Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/15104
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Applied Biology and Chemical Technology | - |
dc.creator | Riordan, JD | en_US |
dc.creator | Keng, VW | en_US |
dc.creator | Tschida, BR | en_US |
dc.creator | Scheetz, TE | en_US |
dc.creator | Bell, JB | en_US |
dc.creator | Podetz-Pedersen, KM | en_US |
dc.creator | Moser, CD | en_US |
dc.creator | Copeland, NG | en_US |
dc.creator | Jenkins, NA | en_US |
dc.creator | Roberts, LR | en_US |
dc.creator | Largaespada, DA | en_US |
dc.creator | Dupuy, AJ | en_US |
dc.date.accessioned | 2015-07-14T01:32:04Z | - |
dc.date.available | 2015-07-14T01:32:04Z | - |
dc.identifier.issn | 1553-7390 | en_US |
dc.identifier.uri | http://hdl.handle.net/10397/15104 | - |
dc.language.iso | en | en_US |
dc.publisher | Public Library of Science | en_US |
dc.rights | © 2013 Riordan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_US |
dc.rights | The following publication Riordan JD, Keng VW, Tschida BR, Scheetz TE, Bell JB, et al. (2013) Identification of Rtl1, a Retrotransposon-Derived Imprinted Gene, as a Novel Driver of Hepatocarcinogenesis. PLoS Genet 9(4): e1003441 is available at https://doi.org/10.1371/journal.pgen.1003441 | en_US |
dc.title | Identification of Rtl1, a Retrotransposon-Derived Imprinted Gene, as a Novel Driver of Hepatocarcinogenesis | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.volume | 9 | en_US |
dc.identifier.issue | 4 | en_US |
dc.identifier.doi | 10.1371/journal.pgen.1003441 | en_US |
dcterms.abstract | We previously utilized a Sleeping Beauty (SB) transposon mutagenesis screen to discover novel drivers of HCC. This approach identified recurrent mutations within the Dlk1-Dio3 imprinted domain, indicating that alteration of one or more elements within the domain provides a selective advantage to cells during the process of hepatocarcinogenesis. For the current study, we performed transcriptome and small RNA sequencing to profile gene expression in SB-induced HCCs in an attempt to clarify the genetic element(s) contributing to tumorigenesis. We identified strong induction of Retrotransposon-like 1 (Rtl1) expression as the only consistent alteration detected in all SB-induced tumors with Dlk1-Dio3 integrations, suggesting that Rtl1 activation serves as a driver of HCC. While previous studies have identified correlations between disrupted expression of multiple Dlk1-Dio3 domain members and HCC, we show here that direct modulation of a single domain member, Rtl1, can promote hepatocarcinogenesis in vivo. Overexpression of Rtl1 in the livers of adult mice using a hydrodynamic gene delivery technique resulted in highly penetrant (86%) tumor formation. Additionally, we detected overexpression of RTL1 in 30% of analyzed human HCC samples, indicating the potential relevance of this locus as a therapeutic target for patients. The Rtl1 locus is evolutionarily derived from the domestication of a retrotransposon. In addition to identifying Rtl1 as a novel driver of HCC, our study represents one of the first direct in vivo demonstrations of a role for such a co-opted genetic element in promoting carcinogenesis. | - |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | Plos genetics, 2013, v. 9, no. 4, e1003441 | en_US |
dcterms.isPartOf | PLoS Genetics | en_US |
dcterms.issued | 2013 | - |
dc.identifier.scopus | 2-s2.0-84876878661 | - |
dc.identifier.pmid | 23593033 | - |
dc.identifier.rosgroupid | r62196 | - |
dc.description.ros | 2012-2013 > Academic research: refereed > Publication in refereed journal | - |
dc.description.oa | Version of Record | en_US |
dc.identifier.FolderNumber | OA_IR/PIRA | en_US |
dc.description.pubStatus | Published | en_US |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
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Riordan_Identification_Rtl1_.pdf | 2.17 MB | Adobe PDF | View/Open |
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